uk one health report · 3 antibiotic use in 2017, a total of 773 tonnes1 of antibiotic active...
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UK One Health Report
Joint report on antibiotic use and
antibiotic resistance, 2013–2017 Published: 31 January 2019
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Suggested citation: Veterinary Medicines Directorate (2019). UK One Health Report - Joint report
on antibiotic use and antibiotic resistance, 2013–2017. New Haw, Addlestone: Veterinary
Medicines Directorate.
Any enquiries or correspondence regarding this publication should be sent to us at:
Veterinary Medicines Directorate Woodham Lane
New Haw, Addlestone
Surrey, KT15 3LS
www.gov.uk/organisations/veterinary-medicines-directorate
Published 31 January 2019
Report contributors Editors-in-Chief
Prof. S. Peter Borriello (Veterinary Medicines Directorate) Dr Susan Hopkins (Public Health England)
Lead authors
Dr Marian Bos (VMD) Dr Berit Muller-Pebody (PHE) Dr Ana Vidal (VMD) Rebecca Guy (PHE)
Contributors
England and Wales
Veterinary Medicines Directorate
Alexandra Pickering Myles Munro Leah Shanks Elizabeth Marier Fraser Broadfoot
Public Health England
Amelia Au-Yeung Katie Hopkins Graeme Rooney Angela Kearns Martin Day Diane Ashiru-Oredope Gauri Godbole Lesley Larkin Alan Johnson Kate Wilson Craig Swift Neil Woodford Emma Budd
Animal and Plant Health Agency
Chris Teale Francesca Martelli
Department for Environment, Food and Rural Affairs
Lee Slater
Environment Agency
Alwyn Hart
Food Standards Agency
Kirsten Stone
Public Health Wales
Laura Evans Margaret Heginbothom Robin Howe
Northern Ireland
Public Health Agency
Paul Cabrey Lynsey Patterson
Agri-Food and Biosciences Institute
Angela Lahuerta-Marin
Department of Agriculture, Environment and Rural Affairs
Ana Pascual
Scotland
Health Protection Scotland
Alison Smith-Palmer Christopher Sullivan Julie Wilson
SRUC Consulting – Veterinary Services
Geoff Foster
Table of contents Executive summary ...................................................................................................................... 2
Chapter 1: Introduction ................................................................................................................ 8
Chapter 2: Antibiotic use ............................................................................................................ 10
2.1 Sales in veterinary and usage in human medicine ..................................................... 10
2.2 Antibiotic usage – international picture ...................................................................... 13
2.3 EU harmonised indicators for use ............................................................................... 16
2.3.1 Animals .................................................................................................................... 16
2.3.2 Humans ................................................................................................................... 17
2.4 Concluding remarks ..................................................................................................... 18
Chapter 3: Antibiotic resistance ................................................................................................ 20
3.1 EU harmonised indicators for AMR ............................................................................. 20
3.1.1 Animals .................................................................................................................... 20
3.1.2 Humans ................................................................................................................... 21
3.2 Resistance in selected bacteria common to animals and humans ........................... 22
3.2.1 Campylobacter spp. ................................................................................................. 22
3.2.2 Non-typhoidal Salmonella spp. ................................................................................ 28
3.2.3 Escherichia coli, including ESBL-, AmpC- and carbapenemase-producers .............. 37
3.2.4 LA-MRSA................................................................................................................. 46
Chapter 4: Antibiotics and AMR in the environment ................................................................ 51
Chapter 5: Discussion ................................................................................................................ 52
References .................................................................................................................................. 55
Annexes ....................................................................................................................................... 60
Annex A List of tables ............................................................................................................ 60
Annex B List of figures ........................................................................................................... 61
Annex C Salmonella serovars ................................................................................................ 63
Annex D Recommendations 2015 UK One Health report ..................................................... 64
Annex E Sources and caveats/limitations of consumption data ......................................... 65
Annex F Methodology AMR data ........................................................................................... 66
Annex G Caveats/limitations of AMR data ............................................................................ 71
Annex H Human biomass and Population Correction Unit .................................................. 74
Annex I Highest Priority Critically Important Antibiotics for human and veterinary
medicine .................................................................................................................................. 75
Annex J Glossary of terms ..................................................................................................... 77
2
Executive summary
Antibiotic Use and Resistance in Animals and People
2013–2017
Antibiotic use
In mg/kg*
Based on use per ‘bodyweight’, there was a reduction of 40% in food-producing animals
(from 62 mg/kg to 37 mg/kg) and 9% in people (from 135 mg/kg to 123 mg/kg).
By weight of active ingredient
Total use/sales in tonnes dropped by 19% from 957 to 773 tonnes.
In 2017, use in people was 491 tonnes and sales for use in animals (food-producing
animals**, horses and pets) were 282 tonnes.
Use in people represented 55% of all use/sales in 2013 and 64% in 2017.
Overall, 89% (17 tonnes) of highest priority critically important antibiotics (HP-CIAs) were
used in people. Their use increased in people by 8% and decreased in animals by 51%.
Antibiotic resistance
For food-producing animals, no resistance was detected in Escherichia coli or Salmonella
spp. to colistin, and very low*** or no resistance was detected respectively to 3rd generation
cephalosporins. There was low resistance level to fluoroquinolones for E. coli and only very
low resistance for Salmonella spp.
For people, resistance level to 3rd generation cephalosporins and to fluoroquinolones was
moderate for E. coli, and was low and moderate respectively for Salmonella spp. Resistance
level to colistin was low in both E. coli and Salmonella spp.
For people, retail chicken meat and food-producing animals, resistance level to
fluoroquinolones was high for Campylobacter jejuni. Resistance to erythromycin was low in
C. jejuni isolates from people and retail chicken meat and very low in isolates from food-
producing animals.
Note:
* mg/kg: is the milligrams of active ingredient of antibiotics sold/used per kilogram of bodyweight of food-
producing animals or people in the UK.
** Food-producing animals include pigs, chickens and turkey for E. coli, chickens and turkeys for C. jejuni
and pigs, broilers, layer chickens and turkeys for Salmonella spp.
*** Resistance levels are classified according to the classification in the European Union summary reports on
antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food, as published by
the European Food Safety Authority. The classification is as follows: <0.1 rare; 0.1–1.0 very low; >1.0–10.0
low; >10.0–20.0 moderate; >20.0–50.0 high; >50.0–70.0 very high; >70.0 extremely high.
Key points
3
Antibiotic Use
In 2017, a total of 773 tonnes1 of antibiotic active ingredients was dispensed in the UK for use in
people and animals. This represents an overall reduction of 19% between 2013 and 2017.
Tonnage used dropped by 6% in people (521 to 4911 tonnes; excluding private prescriptions) and
by 35% in animals (436 to 282 tonnes) over this period.
Of the 773 tonnes, 64% was for use in people, 26% for use in food-producing animals only and
10% for use in companion animals and horses, but also in food-producing animals. Of the 64%
prescribed for human use, approximately 80% was used in the community and 20% in hospitals.
Of the 36% sold for use in animals, 72% was for use in food-producing animals only and 28% for
use in horses, companion animals and also allowed for food-producing animals.
1 For the human sector, use data include all publicly funded prescriptions in primary and secondary care, but not from the
private sector. Therefore, this figure does not cover all human use as there is no method to collect private prescriptions.
Reductions in total tonnes between 2013 and 2017
4
When the tonnage is corrected for bodyweight and population size of humans and animals at the
likely time of treatment, the amount used in people was 123 mg/kg and the amount used in food-
producing animals was 37 mg/kg. This represents a reduction of 9% and 40% respectively when
compared to 2013 levels.
Overall, 19.3 tonnes of antibiotics (2.5% of total UK use) classed as HP-CIAs2 were prescribed or
sold for use in humans and animals of which 89% was used in people and 11% in animals.
Sales of HP-CIAs for use in animals was 2.2 tonnes (0.8% of total sales for use in animals); a drop
of 51% compared to 2013. In people, HP-CIAs use was estimated at 17.1 tonnes (3.5% of total
human use); an increase of 8% compared to 2013.
2 HP-CIAs include the following three classes: 3
rd and 4
th generation cephalosporins, fluoroquinolones and colistin.
Total tonnes of HP-CIAs used between 2013 and 2017
Reductions in mg/kg between 2013 and 2017
5
Antibiotic Resistance
The European Centre for Disease Prevention and Control, the European Food Safety Authority
and the European Medicines Agency have published a recommended set of harmonised primary
and secondary key outcome indicators for monitoring antibiotic resistance in food-producing
animals and humans in the European Union Member States. In the UK, the majority of indicators
have either reduced or were stable between 2013 and 2017.
Indicators for resistance in bacterial isolates from food-producing animals
Indicators for resistance in bacterial isolates from people
EU harmonised key outcome indicators for AMR
E. coli – Escherichia coli S. aureus – Staphylococcus aureus K. pneumoniae – Klebsiella pneumoniae
S. pneumoniae – Streptococcus pneumoniae 3GC – 3
rd generation cephalosporins
AG, FQ – aminoglycosides, fluoroquinolones
6
Ciprofloxacin
In isolates from broilers and turkeys at slaughter and chicken meat at retail, the level of resistance
to ciprofloxacin decreased or remained stable between the two study years, whereas it increased
in people.
Erythromycin
All Campylobacter jejuni isolates obtained from healthy broiler and turkey samples from the
abattoir showed <1% resistance to erythromycin in both year one and two of sampling.
The level of decreased-susceptibility in C. jejuni isolates obtained from retail chicken meat samples
increased from 0% in 2015/2016 to 7.6% in 2017.
In human C. jejuni isolates, non-susceptibility to erythromycin increased from 2.5% in 2015 to 3.4%
in 2017.
Note: Results from healthy animals at slaughter are interpreted using EUCAST human Clinical Breakpoints (CBP); those
from retail meat are interpreted using EUCAST Epidemiological Cut-off values (ECOFF); and results from humans are
interpreted using CBP.
Resistance levels in non-typhoidal Salmonella spp. isolates to HP-CIAs were low (<2%) or not
detected in samples from poultry farms (broilers, layer hens, turkeys) in 2016.
The proportion of human Salmonella spp. isolates tested that were non-susceptible (intermediate
and resistant) to HP-CIAs decreased for colistin (from 6% to 3%), but increased for ciprofloxacin
(from 4% to 14%), cefotaxime (from 1% to 2%) and ceftazidime (from 0% to 4%) between 2013
and 2017. However, this may result from the changes in serovars identified in humans between
2014 and 2017, as well as the change in susceptibility testing practice over this time.
Salmonella spp.
Campylobacter jejuni
7
Between 2014 and 2017, no resistance to the HP-CIAs colistin, cefotaxime and ceftazidime was
detected in E. coli isolates from broilers, turkeys and pigs at slaughter. Resistance levels to HP-
CIA ciprofloxacin were low (<7%) in E. coli isolates from broilers, turkeys and pigs.
In 2017, 1% of human E. coli blood isolates were non-susceptible to colistin, 20% to ciprofloxacin,
and 12% to 3rd generation cephalosporins.
Samples from animals at slaughter and meat at retail were tested for presence of extended-
spectrum β-lactamase (ESBL-) and AmpC β-lactamase (AmpC-) producing E. coli. Between 22%-
25% of pig, 30% of broiler and 5% of turkey samples collected at slaughter yielded ESBL-/AmpC-
producing E. coli. Samples from beef and pork at retail yielded 1-2% ESBL-/AmpC-producing
E. coli; for chicken meat, this was 45%.
None of the E. coli isolates from pigs, broilers and turkeys were presumptive carbapenemase-
producers.
ESBL-/AmpC-/carbapenemase-producing E. coli
Escherichia coli
Chapter 1: Introduction
8
Chapter 1: Introduction Antimicrobial or antibiotic resistance (AMR) is a major cause of concern for human and animal
health, and no single action will provide an adequate solution. Resistant bacteria from animals,
humans and food can be cross-transmitted and environmental reservoirs are a potentially
important source for the mobilisation and transfer of resistance genes. Thus an integrated One
Health approach to AMR surveillance and public health action is needed.
In 2013, the government of the United Kingdom (UK) published the ‘UK five year AMR strategy
2013 to 2018’, setting out actions to slow the development and spread of AMR following a One
Health approach1. In 2016, the Review on Antimicrobial Resistance, commissioned by the UK
government, published its final report and presented ten recommendations to tackle AMR,
including actions on infection prevention and control and reduction of antibiotic use in animals and
humans2. In 2017, the European Commission (EC) published its ‘European One Health Action
Plan against AMR’3.
This is the second UK One Health Report and it includes, in addition to antibiotic use data from
food-producing animals and humans and data on AMR in bacterial isolates from animals and
humans, comparative data on AMR in isolates from retail meat. The aims of the report are to:
Assess occurrence of resistance along the food chain;
Add context to the surveillance data by providing information on control measures in place to
reduce the risk of transmission of the bacteria monitored and policy decisions that have been
taken to tackle AMR.
The report presents the results of AMR monitoring for key zoonotic and indicator bacterial
pathogens for animals and humans: Campylobacter spp., non-typhoidal Salmonella spp.,
Escherichia coli and livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA).
It gives an overview of available data in the context of the One Health approach. Data included in
this report have been presented in more detail in separate annual veterinary and human
surveillance reports, which are referred to in the relevant text.
Certain antibiotic classes are categorised by the World Health Organization (WHO) as critically
important antibiotics for human use. Based on the need to preserve these antibiotics, there are
important ‘One Health’ and antibiotic stewardship considerations for the veterinary sector to take
into account. Therefore, this report focuses on the Highest Priority Critically Important Antibiotics
(HP-CIAs) classified as such by the Antimicrobial Advice ad hoc Expert Group (AMEG) from the
European Medicines Agency (EMA)4, 5, who based their classification on importance to both human
and veterinary medicine. These HP-CIAs are: colistin, fluoroquinolones and 3rd and 4th generation
cephalosporins (see also Annex I).
The previous One Health Report presented ten recommendations (see Annex D)6; progress on
these recommendations is addressed in text boxes throughout this report. Chapter 2 presents data
on antibiotic use in food-producing animals and in humans. Resistance data from bacterial isolates
from food-producing animals, retail meat and humans are presented in Chapter 3. An introduction
to antibiotics and resistance in the environment is included in Chapter 4. A discussion of the data
from a One Health perspective concludes the report in Chapter 5. Technical and background
information can be found in the Annexes.
Chapter 1: Introduction
9
The importance of a One Health approach: colistin resistance
in bacterial isolates from animals, humans and meat
Colistin is used as a last resort antibiotic in human medicine, and used widely in
livestock in parts of the world. In November 2015, the discovery of the plasmid
mediated colistin resistance gene mcr-1 in China was published7; since then other
similar genes have been discovered (e.g. mcr-2, mcr-3)8. The AMEG, reconvened by
the EMA in response to a request by the EC, recommended that colistin should be
added to the AMEG category 2 (higher risk critically important antimicrobials; see
Annex I).
Public Health England’s (PHE) Antimicrobial Resistance and Healthcare Associated
Infections (AMRHAI) Reference Unit analysed archived whole-genome sequences of
~24,000 bacterial isolates submitted to PHE between 2013 and 2015. It identified 15
mcr-1-positive isolates, consisting of ten human Salmonella enterica and three
human Escherichia coli isolates, as well as two Salmonella Paratyphi B var Java
isolates from poultry meat imported in 20149. Since starting screening in 2016,
AMRHAI has identified three additional mcr-1-positive strains among referred human
colistin-resistant isolates. In the period since the last report (2014 to 2017), there has
been a total of 302 colistin-resistant non-typhoidal Salmonella spp. or E. coli isolates
from humans reported, and 32 non-typhoidal Salmonella spp. with plasmid-mediated
resistance gene mcr-1 identified.
In response to the discovery of the mcr-1 gene, overall colistin use in food-producing
animals in the UK decreased by 99% between 2015 and 2017 to 0.001 mg/kg10. This
was the result of various livestock sectors voluntarily stopping or restricting the use
of colistin. Based on the electronic Medicine Book Pigs (eMB Pigs), colistin use in
pigs was 0.01 mg/kg in 2017, a 99% decrease from 201510. According to data from
the British Poultry Council (BPC), colistin use in meat poultry in the UK reduced from
40 kg in 2015 to 8 kg in 2016, after which they voluntarily stopped its use in this
livestock sector11, 12.
All E. coli and Salmonella spp. isolated from food-producing animals under the
framework of the EU harmonised AMR monitoring are tested for susceptibility to
colistin. Since 2016, the Animal and Plant Health Agency (APHA) also performs
enhanced colistin resistance testing on these E. coli isolates from England, Scotland
and Wales, through additional selective culture methods. Between 2014 and 2017,
no resistance to colistin was detected in the bacterial (Salmonella spp. and E. coli)
isolates obtained and tested under the EU monitoring from healthy broiler chickens,
turkeys or pigs at slaughter, and pork and broiler meat at retail.
Chapter 2: Antibiotic use
10
Chapter 2: Antibiotic use
2.1 Sales in veterinary and usage in human medicine In 2017, the total UK antibiotic consumption in humans and animals was 773 tonnes of active
ingredient. Of this total, 282 tonnes (36%) were antibiotics sold for use in animals; 204 tonnes
(26% of the total UK antibiotic consumption) were antibiotics authorised for use in food-producing
animals only (72% of total animal use), 51 tonnes (7%) for use in food-producing animals,
companion animals and horses, and 27 tonnes (3%) for use in companion animals and horses only
(Figure 1). The other 491 tonnes (not including all data from the private sectorc; 64%) were
antibiotics prescribed for humans: 80% was prescribed in the community and 20% in the hospital
sector. This represents an average 19% reduction in total tonnes of antibiotic active ingredient sold
for use in animals and prescribed for humans in the UK between 2013 and 2017 with a 35%
reduction in animal and a 6% reduction in human sectors over this time period (Table 1).
Figure 1: Proportion of tonnes of active ingredient prescribed for humans and sold for use in
animals in the UK; 201710
Antibiotic usage data by species are being collected by some animal production sectors and these
data are voluntarily provided for inclusion in the annual UK-VARSS reports10. However, usage data
is not available for all sectors and production coverage is variable. For the purpose of this One
Health Report the sales data of antibiotics for use in veterinary medicine are provided, which cover
all animals in the UK. These data have been published annually since 1998, and are used to
monitor trends in use and to inform policy on AMR.
Human health surveillance in the UK does not collect sales data for antibiotics used in human
medicine; its antibiotic use data warehouse is a repository for national antibiotic prescribing data
collated from primary and secondary care. This allows PHE to monitor trends in antibiotic use and
c This includes data from all publicly funded prescriptions in primary and secondary care but not all from the private
sector (private community or solely private hospitals). Therefore, this figure does not cover all human use as there is no method to collect private prescriptions. In the previous Report use from the private sector was estimated to add around 10% on top of human consumption data, but it is not possible to confirm that it is still the same proportion for 2017.
Community80%
Hospitals20%
Animals36%
Humans64%
Food-producing animals
only72%
Horses, companion and food-producing animals
18%
Horses and
companion animals
only10%
Chapter 2: Antibiotic use
11
publish prescribing indicators at an increasing level of data granularity. The published indicators
are being used by healthcare staff, commissioners, academics and the public to measure and
evaluate the impact of National Health Service (NHS) quality initiatives, develop local AMR action
plans, inform antibiotic stewardship activities and/or to compare antibiotic usage between peer
groups, for example GP surgeries or NHS Trusts.
The antibiotic groups most sold for use in animals are tetracyclines, followed by penicillins, and
trimethoprim/sulphonamide combinations (Table 1). The biggest percentage reductions in sales
between 2013 and 2017 were for colistin (99% reduction), fluoroquinolones (50%), trimethoprim/
sulphonamides (49%), lincosamides (47%), tetracyclines (46%) and macrolides (42%). An
increase of 89% was seen for sales of amphenicols (from 2.6 to 4.9 tonnes) between 2013 and
2017, which may be a result of replacement of HP-CIAs with, for example, florfenicol. However,
this antibiotic class accounted only for <2% of total sales in 2017. The overall reduction between
2013 and 2017 for sales of antibiotics for veterinary use was 35%. Another increase (46%) was
seen for sales of aminoglycosides.
Table 1: Total systemic antibiotics prescribed in humans from primary and secondary care and
quantity of antibiotics sold for use in food-producing animals in the UK, expressed in tonnes active
ingredient and percentage of the total; 2013–201710
Antibiotics prescribed
in humansa (tonnes (%))
Antibiotics sold for use in animalsb
(tonnes (%))
Antibiotic group 2013 2017 2013 2017
Penicillins 339.1 (65) 330.2 (67) 87.5 (20) 72.5 (26)
Tetracyclines 54.6 (10) 48.2 (10) 194 (44) 104.9 (37)
Macrolides 54.5 (10) 43.5 (9) 40.3 (9) 23.3 (8)
Trimethoprim/sulphonamides 24.0 (5) 17.4 (4) 60.7 (14) 31.0 (11)
1st and 2nd generation cephalosporins 17.4 (3) 13.3 (3) 4.9 (1) 4.1 (1)
Fluoroquinolones 12.1 (2) 12.0 (2) 2.6 (0.6) 1.3 (0.5)
Other antibacterials*¥ 7.9 (2) 10.4 (2) 20.4 (5) 13.7 (5)
3rd and 4th generation cephalosporins 3.4 (0.7) 4.5 (0.9) 1.2 (0.3) 0.9 (0.3)
Monobactams, carbapenems‡ 3.4 (0.7) 4.0 (0.8) 0 (0) 0 (0)
Lincosamides 2.3 (0.4) 3.1 (0.6) 6.2 (1) 3.3 (1)
Glycopeptides‡ 1.4 (0.3) 1.9 (0.4) 0 (0) 0 (0)
Aminoglycosides 0.9 (0.2) 0.8 (0.2) 14.8 (3) 21.6 (8)
Polymyxins (incl. colistin) 0.4 (0.1) 0.6 (0.1) 0.7 (0.2) 0.007 (0)
Amphenicols 0.1 (0) 0.1 (0) 2.6 (0.6) 4.9 (2)
Other quinolones‡ 0.0 (0) 0.0 (0) 0 (0) 0 (0)
TOTAL 521.4 (100) 491.0 (100) 436.0 (100) 281.6 (100) a ERRATUM: Please note that an error was identified in the figures published for total systemic antibiotics prescribed in
humans from primary and secondary care in the UK One Health report 2015. The translation of colistin from Defined
Daily Doses to weight was calculated incorrectly and revision of the ATC index meant changes to units which were
applied to the retrospective figures calculated for this year’s report. Please take this into account when comparing
antibiotic consumption data for humans presented in the 2015 One Health Report with the 2019 report; b Figures differ
from the previous One Health Report as the methodology has been adapted to the ESVAC methodology; historical
figures have been retrospectively calculated following the same method; * Other (humans): nitrofurantoin, fusidic acid,
metronidazole, fosfomycin, methenamine/hippurate, linezolid. Additionally, two oral agents outside the ‘J01’ group
(fidaxomicin [A07AA12], vancomycin [A07AA09]) which are used to treat Clostridium difficile infections were included; ¥
Other (animals): bacitracin, fosfomycin, furaltadone, metronidazole, novobiocin, paromomycin, rifaximin; ‡ There are no
authorised veterinary medicines which contain antibiotics from these classes.
Chapter 2: Antibiotic use
12
The combined primary and secondary care consumption of systemic antibiotics (ATC groups J01,
A07AA) was 491 tonnes active ingredient in the human sector in the UK in 2017, a decline of 30
tonnes (6%) since 2013. The breakdown by antibiotic groups is shown in Table 1. In terms of
tonnes of active ingredient, the antibiotic group most prescribed in humans are the penicillins
(around two thirds of the total weight of drugs consumed), followed by tetracyclines and macrolides
(Table 1). Total consumption decreased for penicillins, tetracyclines, macrolides, trimethoprim/
sulphonamides, 1st and 2nd generation cephalosporins and fluoroquinolones, but increased for
antibiotics grouped as ‘other’ (see for definition Table 1), colistin, 3rd and 4th generation
cephalosporins, lincosamides and glycopeptides in the UK between 2013 and 2017.
Caution is advised in interpreting these data as the Defined Daily Dose (DDD) of any given drug
varies considerably and thus weight may not accurately reflect the prevalent consumption of a
particular drug. For more detailed information on antibiotic consumption trends in the UK human
sector please consult the national reports for England13, Wales14, Northern Ireland15 and
Scotland16.
Figure 2 shows the year-over-year changes in tonnage of the HP-CIAs prescribed/sold in the
human and veterinary sector respectively in the UK between 2013 and 2017. The tonnage of active
ingredient sold for use in food-producing animals has mostly reduced over the period 2013–2017,
whereas the tonnage used in the human sectors fluctuated over the same period. When comparing
tonnes of active ingredient of 3rd and 4th generation cephalosporins, fluoroquinolones and colistin,
the majority (89%) is prescribed for humans, although more colistin was sold for use in animals in
2013 (Table 1). Overall, the use of HP-CIAs increased by 8% in humans and decreased by 51% in
animals between 2013 and 2017.
Figure 2: Year-over-year change in tonnes of active ingredient of HP-CIAs prescribed for humans
and sold for use in animals in the UK; 2013–2017
-1
-0.8
-0.6
-0.4
-0.2
0
0.2
0.4
0.6
0.8
20
13-2
014
20
14-2
015
20
15-2
016
20
16-2
017
20
13-2
014
20
14-2
015
20
15-2
016
20
16-2
017
20
13-2
014
20
14-2
015
20
15-2
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20
16-2
017
3rd and 4th generationcephalosporins
Fluoroquinolones Colistin*
Ch
an
ge i
n t
on
nes o
f acti
ve i
ng
red
ien
t
Animals Humans
* No changes in amount of colistin prescribed for use in human medicine between 2013 and 2016
To enable comparisons across human and animal data, the weight of the total UK human
population was calculated, using the methodology described in Annex H. A similar measure was
calculated for the biomass of the food-producing animal species. As only food-producing animals
are included in this measure, the corresponding mass of active ingredient was calculated including
only antibiotics authorised for use in these species. The calculated mass of active ingredient was
Chapter 2: Antibiotic use
13
then converted to milligrams per kilogram estimated biomass for both populations. In 2017,
consumption of antibiotics in food-producing animals was 37 mg/kg (down 40% from 62 mg/kg in
2013) and consumption of systemic and intestinal antibiotics in humans equated 123 mg/kg (down
9% from 135 mg/kg in 2013).
Monitoring of antibiotic residues in meat
Council Directive 96/23/ECd requires each European Union Member State (MS) to
carry out an annual surveillance programme (National Residues Control Plan). Of all
bovine, porcine, ovine, caprine and equine animals, 0.4% must be tested – this
equates to approximately 30,000 samples per annum. Annexes I and II of 96/23/EC
set out the groups of veterinary residues that MSs are obliged to test for: 0.25% is
apportioned to unauthorised substances, with the remaining 0.15% covering
veterinary drugs and contaminants; antibiotics fall under this particular remit. The
total number of tests to be taken for antibiotics from the 0.15% figure varies
according to species (outlined in 96/23/EC). Over 30 different antibiotic substances
are tested for in the plan throughout the calendar year. Each analysed test
undergoes a screening and confirmatory process at the National Reference
Laboratories (NRL), Fera and the Agri-Food and Biosciences Institute (AFBI). The
procedures adopted at the NRL for the validation of both confirmatory and screening
methods of antibiotics and all other substances are set out in accordance with
Commission Decision 2002/657/ECe.
In 2017, 6,399 samples were analysed for antibiotic residues, 19 (0.3%) of which
were non-compliant (covering a range of antibiotics, for example tetracyclines,
macrolides and amphenicols, but no HP-CIAs). Findings on the causality of non-
compliant results are published on a bi-monthly basis at https://www.gov.uk/
government/collections/residues-statutory-and-non-statutory-surveillance-results.
2.2 Antibiotic usage – international picture An overview of antibiotic consumption in food-producing animals for all participating European
countries can be found in the annual European Surveillance of Veterinary Antimicrobial
Consumption (ESVAC) reports on the EMA’s website17. The European Surveillance of
Antimicrobial Consumption Network (ESAC-Net) publishes annual reports on antimicrobial
consumption data for the community and for the hospital sector provided by EU MSs and two EEA
countries18.
Figure 3 is derived from the most recent ESVAC report and shows the total amount of antibiotics
sold for use in food-producing animals in Europe in 2016, expressed in milligrams/Population
Correction Unit (mg/PCU)17. In comparison with other ESVAC participating countries, the UK is
ranked 10th of 30 (1 being lowest usage) within Europe. The total sales of antibiotics for food-
producing animals were 45 mg/PCU in 2016. In 2017, the total sales for food-producing animals in
the UK had further reduced to 37 mg/PCU.
d https://eur-lex.europa.eu/legal-content/EN/ALL/?uri=CELEX%3A31996L0023
e https://eur-lex.europa.eu/legal-content/EN/ALL/?uri=CELEX%3A32002D0657
Chapter 2: Antibiotic use
14
Figure 3: Quantity of antibiotics sold for use in food-producing animals for 30 European countries
as reported by ESVAC; mg active substance sold per population correction unit (mg/PCU); 201617
0 50 100 150 200 250 300 350 400 450
Norway
Iceland
Sweden
Finland
Latvia
Slovenia
Luxembourg
Lithuania
Denmark
United Kingdom
Austria
Switzerland
Slovakia
Ireland
Netherlands
Czech Republic
Greece
Estonia
France
Romania
Germany
Croatia
Poland
Belgium
Bulgaria
Hungary
Portugal
Italy
Spain
Cyprus
Total sales in food-producing animals in 2016 (mg/PCU)
Progress on recommendation 8 of the 2015 report
“VMD will participate in the protocol development of the European Surveillance of Veterinary
Antimicrobial Consumption (ESVAC) project to collect farm level data from the pig sector; and
investigate and facilitate options for collecting accurate antimicrobial consumption data at an
individual farm level.”
During 2014–2015, the VMD participated in a trial for collecting data on use of
antibiotics in pigs for the ESVAC project of the EMA. Furthermore, a representative
for the VMD acts as member of the ESVAC ‘by species’ Expert Advisory Group,
which drafted guidance on the collection of antibiotic use data by species19.
In addition, the VMD supports the development of datasets on antibiotic usage in a
growing number of animal production sectors. These data are voluntarily provided by
the animal production sectors for inclusion in the annual UK – Veterinary
Antimicrobial Resistance and Sales Surveillance (UK-VARSS) reports10.
Chapter 2: Antibiotic use
15
Figure 4 shows the data as presented by the most recent ESAC-Net report for consumption of
antibiotics for systemic use in the community and hospital sector in Europe in 2017. The combined
rate (expressed as DDD per 1,000 inhabitants per day) of antibiotic consumption in the UK in 2017
was 21.7; this ranged between 11.0 and 39.7 for all countries18. In comparison with other ESAC-
Net participating countries, this puts the UK at 19th of 28 (1 being lowest usage) within Europe.
However, caution is needed in interpreting this information as comparison is made against other
countries and not a benchmark.
Figure 4: Consumption of antibiotics for systemic use (ATC group J01) in the community and
hospital sector in Europe as reported by ESAC-Net; 201718
0 5 10 15 20 25 30 35 40 45
Netherlands
Estonia
Austria#
Slovenia
Sweden
Germany#
Latvia
Finland
Lithuania
Norway
Denmark
Hungary
Portugal
Croatia
Iceland#
Bulgaria
Italy
Ireland
United Kingdom
Belgium
Luxembourg
Malta
Spain
Poland
Cyprus*
Romania*
France
Greece
Total consumption in humans in 2016 (DDD per 1,000 inhabitants per day)
* Country only provided total care data; # country provided no hospital data
Chapter 2: Antibiotic use
16
2.3 EU harmonised indicators for use September 2017 saw the publication by the European Centre for Disease Prevention and Control
(ECDC), European Food Safety Authority (EFSA) and EMA of a recommended set of harmonised
key outcome indicators for monitoring antibiotic consumption in the EU MSs. The rationale for the
selection of these indicators is described in more detail in the joint working group paper20. Results
for the UK are presented in this chapter.
2.3.1 Animals
The EU harmonised primary outcome indicator for antibiotic consumption in food-producing
animals is:
Overall sales of veterinary antibiotics in milligrams of active substance per kilogram of
estimated weight at treatment of livestock and of slaughtered animals in a country (mg/PCU).
The secondary indicators are:
Sales in mg/PCU for 3rd and 4th generation cephalosporins;
Sales in mg/PCU quinolones (and percentage of fluoroquinolones);
Sales in mg/PCU for polymyxins.
In the UK all quinolones sold for use in food-producing animals are fluoroquinolones.
Figure 5 shows the outcome indicators for antimicrobial consumption in food-producing animals in
the UK over the period 2013–2017. All indicators showed a reduction between 2013 and 2017.
Total sales reduced by 40% (from 62 mg/PCU to 37 mg/PCU). Sales of 3rd and 4th generation
cephalosporins decreased by 32% (from 0.18 mg/PCU to 0.12 mg/PCU), sales of quinolones
decreased by 55% (from 0.36 mg/PCU to 0.16 mg/PCU) and sales of colistin decreased by 99%
(from 0.11 mg/PCU to 0.001 mg/PCU).
Figure 5: EU harmonised primary (total sales of veterinary antibiotics in mg/PCU) and secondary
(sales in mg/PCU for 3rd and 4th generation cephalosporins, quinolones and polymyxins) outcome
indicators for antibiotic consumption in food-producing animal species in the UK; 2013–2017
0
10
20
30
40
50
60
70
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0.40
2013 2014 2015 2016 2017
To
tal s
ale
s (m
g/P
CU
)S
ale
s p
er
an
tib
ioti
c c
lass (
mg
/PC
U)
3rd and 4th Generation cephalosporins Quinolones Polymyxins Total
Chapter 2: Antibiotic use
17
2.3.2 Humans
For the human sector, the primary and secondary indicators listed below have been recommended
jointly by ECDC, EFSA and EMA to assess progress in reducing the use of antibiotics. The
indicators aim to capture the selective pressure of specific antibiotic classes on the development of
antibiotic resistance, facilitate monitoring the use of critically important antibiotics and the effect of
antibiotic stewardship initiatives.
Primary indicator:
Total consumption of antibiotics for systemic use (ATC group J01) – in hospitals and the
community – expressed as defined daily doses (DDD) per 1,000 inhabitants and per day.
Secondary indicators:
Ratio of consumption of broad-spectrum penicillins, cephalosporins, macrolides (except
erythromycin) and fluoroquinolones to the consumption of narrow-spectrum penicillins,
cephalosporins and erythromycin in the community;
Proportion of total hospital consumption of glycopeptides, 3rd and 4th generation
cephalosporins, monobactams, carbapenems, fluoroquinolones, polymyxins, piperacillin and
enzyme inhibitor, linezolid, tedizolid and daptomycin.
Total consumption of systemic antibiotics has fallen (5.2%) in the UK between 2013 and 2017 from
22.9 to 21.7 DDD per 1000 population per day (Figure 6). Over the same time period the ratio of
broad-spectrum antibiotic consumption compared to narrow-spectrum antibiotic consumption
changed from 0.42 to 0.46 in the community and the consumption of broad-spectrum antibiotics in
hospitals, measured as a proportion of the total hospital consumption, increased from 15.1% until
2016 (16.6%) followed by a decrease to 15.7% in 2017 (Figure 7).
Figure 6: EU harmonised primary indicator: total consumption of antibiotics for systemic use in
humans (DDD per 1,000 inhabitants and per day) in the UK; 2013–2017
20.5
21.0
21.5
22.0
22.5
23.0
23.5
2013 2014 2015 2016 2017
DD
D p
er
1,0
00 i
nh
ab
itan
ts p
er
day
Chapter 2: Antibiotic use
18
Figure 7: EU harmonised secondary indicators: ratio of the community consumption of broad-
spectrum penicillins, cephalosporins, macrolides (except erythromycin) and fluoroquinolones to the
consumption of narrow-spectrum penicillins, cephalosporins and erythromycin, and proportion of
total hospital antibiotic consumption that are glycopeptides, 3rd and 4th generation cephalosporins,
monobactams, carbapenems, fluoroquinolones, polymyxins, piperacillin and enzyme inhibitor,
linezolid, tedizolid and daptomycin (DDD per 1,000 inhabitants per day) in the UK; 2013–2017
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
16.0
18.0
20.0
2013 2014 2015 2016 2017
Rati
o (
co
mm
un
ity i
nd
icato
r)
Pro
po
rtio
n (
ho
sp
ital
ind
icato
r)
(DD
D p
er
1,0
00 in
hab
itan
ts p
er
day)
Secondary Indicator (Hospital) Secondary Indicator (Community)
2.4 Concluding remarks There was a large decrease in sales of veterinary antibiotics between 2013 and 2017, ranging
between 16% and 99% for each antibiotic class with 35% reduction overall. Sales of HP-CIAs for
use in animals were very low in 2017, and have decreased by 51% since 2013. Prescriptions for
use of antibiotics in humans also showed an overall decrease (6%), with decreases in use for most
antibiotic classes. Use of HP-CIAs is low in humans. When comparing amounts of active ingredient
used for animals and for humans, the largest proportion of HP-CIAs was prescribed for use in
humans in 2017. Compared to other European countries, the UK has below average antibiotic use
in both the animal and human sector.
Chapter 2: Antibiotic use
19
Antibiotic stewardship from a One Health perspective
Since 2014, PHE has worked in collaboration with the VMD on the Antibiotic Guardian
campaign, which is a pledge-based behaviour change strategy. Since the start of the
Antibiotic Guardian campaign, the website has been visited 470,968 times. This has
translated into over 55,000 pledges (see figure below).
Case studies of antibiotic stewardship activities in human and animal health which
were shortlisted entries for the Antibiotic Guardian Awards following peer review are
available through the shared learning platform (www.antibioticguardian.com/shared-
learning). The awards celebrate the work of healthcare professionals across England in
tackling antibiotic resistance and protecting antibiotic usage. At the Antibiotic
Guardian’s gala event held in London in June 2018, awards were presented, among
others, to Bristol Veterinary School (Agriculture and Food category), RUMA
(Responsible Use of Medicines in Agriculture Alliance; Community Communications
and Prescribing & Stewardship categories), NHS Sunderland CCG (Diagnostic
Stewardship category), and King’s College London (Student of the Year category),
reflecting the ‘One Health’ approach of the Antibiotic Guardian campaign.
Antibiotic Guardian pledges (%) by target group in the UK, 2014–2017
Chapter 3: Antibiotic resistance
20
Chapter 3: Antibiotic resistance
3.1 EU harmonised indicators for AMR The ECDC, EFSA and EMA have published a recommended set of harmonised key outcome
indicators for monitoring antibiotic resistance in the EU MSs. The rationale for the selection of
these indicators is described in more detail in the joint working group paper20. Results for the UK
are presented in this chapter.
3.1.1 Animals
The primary summary indicator for AMR in food-producing animals in a country is:
Proportion of indicator E. coli isolates from broilers, fattening turkeys, fattening pigs and
calves (as collected under the framework of Commission Implementing Decision
2013/652/EUf), weighted by the size (expressed in PCU) of the four animal populations, that
are fully susceptible to the entire panel of antibiotics defined in the Decision.
The secondary indicators are:
Proportion of indicator E. coli isolates from broilers, fattening turkeys, fattening pigs and
calves, weighted by PCU, that shows decreased-susceptibility to at least three antibiotics
from different classes from the predefined panel of antibiotics;
Proportion of indicator E. coli isolates from broilers, fattening turkeys, fattening pigs and
calves, weighted by PCU, that are microbiologically resistant to ciprofloxacin;
Proportion of samples identified as positive for presumptive ESBL-/AmpC-producing indicator
E. coli in the framework of the specific monitoring for ESBL-/AmpC-/carbapenemase-
producing indicator E. coli from broilers, fattening turkeys, fattening pigs and calves,
weighted by PCU.
In the UK, the veal industry does not reach the threshold of 10,000 tonnes of meat produced per
year, and therefore is excluded for the EU AMR monitoring programme. Due to the sampling
schedule the indicators can only be expressed for any combination of two consecutive calendar
years.
The primary indicator for the UK showed that the proportion of fully susceptible E. coli increased by
30% between 2014/2015 and 2016/2017, from 18% to 23%, indicating there was an increase in the
level of susceptibility in relation to the biomass of food-producing animals (Figure 8).
The secondary indicators also showed an increase in the level of susceptibility (Figure 8). The
proportion of indicator E. coli isolates that shows decreased-susceptibility to at least three
antibiotics from different classes from the predefined panel of antibiotics decreased by 20% from
57% to 45%. The proportion of indicator E. coli isolates that are microbiologically resistant to
ciprofloxacin showed a 7% reduction from 15% to 14%. Lastly, the proportion of samples identified
as positive for presumptive ESBL-/AmpC-producing indicator E. coli decreased by 5% between
2015/2016 and 2016/2017, from 26% to 25%.
f https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A32013D0652
Chapter 3: Antibiotic resistance
21
Figure 8: Recommended primary (proportion of fully susceptible E. coli isolates) and secondary
indicators (proportion of presumptive ESBL-/AmpC-producing E. coli isolates, proportion of
multiple-resistant E. coli isolates and proportion of E. coli isolates microbiologically resistant to
ciprofloxacin) for the animal AMR monitoring in the UK; 2014–2017
0%
10%
20%
30%
40%
50%
60%
20
14/1
5
20
15/1
6
20
16/1
7
20
14/1
5
20
15/1
6
20
16/1
7
20
14/1
5
20
15/1
6
20
16/1
7
20
14/1
5
20
15/1
6
20
16/1
7
Fully susceptibleE. coli
Presumptive ESBL-/AmpC-producing E. coli*
Multiple-resistantE. coli
Ciprofloxacin-resistantE. coli
Pro
po
rtio
n
Indicator
Primary indicator Secondary indicator
* Data not available for 2014/2015
3.1.2 Humans
In humans the primary antibiotic resistance indicators are:
Proportion of methicillin-resistant Staphylococcus aureus among S. aureus isolates;
Proportion of 3rd generation cephalosporin-resistant E. coli.
The primary indicators for the UK showed that the proportion of E. coli resistant to 3rd generation
cephalosporins decreased between 2013 and 2017 from 15% to 10% (30% reduction), and a 50%
reduction in proportion of MRSA in humans was seen over the same time period, from 14% to 7%
(Figure 9).
The secondary antibiotic resistance indicators for human surveillance reflect key areas for
monitoring in the international as well as domestic hospital and community sectors; these are:
Proportion of Klebsiella pneumoniae resistant to aminoglycosides, fluoroquinolones and 3rd
generation cephalosporins;
Proportion of K. pneumoniae resistant to carbapenems;
Proportion of Streptococcus pneumoniae resistant to macrolides;
Proportion of S. pneumoniae resistant to penicillins.
There was a reduction in resistance in two of the secondary indicators between 2013 and 2017.
The proportion of K. pneumoniae resistant to aminoglycosides, fluoroquinolones and 3rd generation
cephalosporins reduced by 13% between 2013 and 2017, from 4.8% to 4.2%, and the proportion of
Streptococcus pneumoniae resistant to macrolides reduced from 6.7% to 5.6%, a 16% reduction.
The other two secondary indicators increased slightly over the same time period, but remain ≤1%
resistant: the proportion of S. pneumoniae resistant to penicillins was 1% in 2017, and the
proportion of K. pneumoniae resistant to carbapenems was <1% (Figure 9).
E. coli E. coli E. coli E. coli*
Chapter 3: Antibiotic resistance
22
Figure 9: Recommended primary (proportion of 3rd generation cephalosporin-resistant E. coli
isolates and proportion of MRSA among S. aureus isolates) and secondary indicators (proportion
of K. pneumoniae resistant to fluoroquinolones, 3rd generation cephalosporins and
aminoglycosides, proportion of K. pneumoniae resistant to carbapenems, proportion of
S. pneumoniae resistant to penicillins and proportion of S. pneumoniae resistant to macrolides) for
the human health AMR monitoring in the UK; 2013–2017*
0
2
4
6
8
10
12
14
16
20
13
20
14
20
15
20
16
20
17
20
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20
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20
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20
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17
MRSAof S. aureus
E. coliresistantto 3GC
K. Pneumoniaeresistant to AG,
FQ and 3GC
S. pneumoniaeresistant topenicillins
S. pneumoniaeresistant tomacrolides
K. pneumoniaeresistant to
carbapenems
Pro
po
rtio
n (
%)
Indicator
Series1 Primary indicator Secondary indicator
* Data are taken from the ECDC Surveillance Atlas – Antimicrobial Resistance and reflect UK data as reported through
the EARS-Net surveillance programme. This surveillance does not include all laboratories within the UK;
AG = aminoglycosides; FQ = fluoroquinolones; 3GC = 3rd
generation cephalosporins
3.2 Resistance in selected bacteria common to animals and humans
3.2.1 Campylobacter spp.
3.2.1.1 Background
Campylobacter are commensal bacteria which are common in poultry and pigs, and a zoonotic
pathogen. They are the most common cause of human foodborne bacterial disease in the UK,
estimated to cause more than 280,000 cases each year21. Handling, preparation and consumption
of contaminated broiler meat has been identified as one of the main sources of human infection. In
humans, the symptoms usually occur two to five days after infection and are often mild and self-
limiting. Antibiotic treatment is not usually required but severe cases may be treated with a
macrolide antibiotic (e.g. clarithromycin, azithromycin, erythromycin) with a move away from using
ciprofloxacin, as resistance to quinolones is now considered to be too high for these antibiotics to
be used for empirical treatment22.
3.2.1.2 Resistance – food-producing animals
Compared to 2014, in 2016 the percentage of resistance (interpreted using European Committee
for Antimicrobial Susceptibility Testing – EUCAST – human clinical breakpoints; CBPs) in
Campylobacter jejuni isolated from broiler caecal samples (collected at slaughter under the EU
AMR monitoring scheme, see Annex F) slightly decreased for ciprofloxacin (from 44% to 41%) and
E. coli S. aureus
K. pneumoniae K. pneumoniae S. pneumoniae S. pneumoniae
Chapter 3: Antibiotic resistance
23
remained very low for erythromycin (<1%); ciprofloxacin was a previously recommended treatment
option for severe cases of campylobacteriosis in human medicine.
A similar pattern was seen in C. jejuni isolates obtained from turkey caecal samples in 2014 and
2016, with a stable level of resistance to ciprofloxacin (35%) and very low resistance to
erythromycin (≤1%) (Figure 10).
Figure 10: Percentage resistance (interpreted using EUCAST human CBPs) in C. jejuni isolates
from caecal samples taken at slaughter from broiler chickens and turkeys in the UK (EU
harmonised monitoring); 2014 and 201611
%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Ciprofloxacin Erythromycin Tetracycline
Resis
tan
t is
ola
tes
Broiler 2014 (n=165) Broiler 2016 (n=180) Turkey 2014 (n=157) Turkey 2016 (n=190)
Other antibiotics were included in the panel for susceptibility testing in accordance with Decision
2013/652/EU, which based the prioritisation on whether the antimicrobial was considered to be
relevant for human therapeutic use and/or epidemiologically relevant to be able to monitor and/or
detect new resistance mechanisms of public health importance23.
The percentage of broiler isolates showing resistance to tetracycline in 2016 was similar to 2014
(58% in 2014 compared to 56% in 2016). The proportion of broiler isolates showing decreased-
susceptibility (interpreted using EUCAST epidemiological cut-off values; ECOFFs) to nalidixic acid
was lower in 2016 compared to 2014 but still high (from 44% in 2014 to 41% in 2016). Decreased-
susceptibility to gentamicin and streptomycin was not detected, or was low, in broiler isolates from
both years (≤1%). In turkey isolates, there was less resistance to tetracycline in 2016 compared to
2014 (42% and 65%, respectively). The level of decreased-susceptibility to nalidixic acid was high
in both years (35% and 33%). There were low levels of decreased-susceptibility to gentamicin
(≤1%) and streptomycin (<2%) in turkey isolates for both years (Figure 10).
3.2.1.3 Resistance – retail meat
A survey of whole, UK-produced fresh chicken at retail during the period February 2014 to March
2015 tested 4,011 samples; 73% of the samples yielded Campylobacter spp.24. A subset of the
C. jejuni (n=230) and C. coli (n=53) isolates were tested to determine the antibiotic resistance
profiles (interpreted using breakpoints, see Annex F for methodology).
Resistance to ciprofloxacin was detected in 49% of the C. jejuni isolates and 55% of the C. coli
isolates tested. Resistance to erythromycin was higher in C. coli isolates (11%) than in C. jejuni
isolates (<1%) (Figure 11).
Chapter 3: Antibiotic resistance
24
Figure 11: Percentage resistance (interpreted using breakpoints) in C. jejuni and C. coli isolates
from retail chicken meat in the UK; 2014–201524,25
%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Ciprofloxacin Erythromycin Nalidixic acid Streptomycin Tetracycline
Resis
tan
t is
ola
tes
C. jejuni (n=230) C. coli (n=53)
A high level of resistance to nalidixic acid and tetracycline was detected in isolates from both
Campylobacter species (51%–68%). All isolates were susceptible to gentamicin, neomycin and
kanamycin (results not shown), and 24% of C. jejuni and 28% of C. coli isolates were susceptible
to all antibiotics tested.
A subsequent study determined antibiotic susceptibility in 437 C. jejuni and 108 C. coli isolates
from 2,998 samples from whole, UK-produced fresh chicken at retail during the period July 2015 to
May 201626. During September and October 2017, 157 C. jejuni and 45 C. coli isolates obtained
from 79 samples of fresh or frozen raw chicken (whole and portioned), collected at retail, were
tested for antibiotic susceptibility27.
A smaller proportion of C. jejuni and C. coli isolates showed decreased-susceptibility to
ciprofloxacin in 2017 (39% and 47%, respectively) than in 2015/16 (54% and 48%, respectively),
but the proportion increased for erythromycin (7% and 8%, respectively, in 2017 vs. 0 and 2%,
respectively, in 2015/16) (Figure 12).
The 2017 C. coli isolates also showed a larger proportion (67%) of decreased-susceptibility to
nalidixic acid than the 2015/16 isolates (50%). For the other antibiotics tested, the proportions of
isolates with decreased-susceptibility were smaller in 2017 than in 2015/16 (see Figure 12).
Differences in the levels of susceptibility to ciprofloxacin and tetracycline between isolates from
standard and organic birds were examined for the 2015/2016 data. No significant differences were
found, however the small sample size, especially for organic chickens (18 organic, 76 free range
and 454 standard chicken samples), may have limited the ability to detect important differences
where they may exist.
C. jejuni C. coli
Chapter 3: Antibiotic resistance
25
Figure 12: Percentage isolates with decreased-susceptibility (interpreted using EUCAST ECOFFs)
in C. jejuni and C. coli strains isolated from retail chicken meat in the UK; 2015–201726, 27
%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Ciprofloxacin Erythromycin Gentamicin Nalidixic acid Streptomycin Tetracycline
Iso
late
s w
ith
decre
ased
-su
scep
tib
ilit
y
C. jejuni 2015/16 (n=437) C. jejuni 2017 (n=157)
C. coli 2015/16 (n=108) C. coli 2017 (n=45)
3.2.1.4 Resistance – humans
The number of Campylobacter spp. isolates reported through routine laboratory surveillance from
humans in the UK in 2017 was 60,408, a 7% decrease from the 64,764 isolates reported in 2013.
Laboratory guidance does not currently recommend identification of Campylobacter spp. to species
level unless clinically indicated. As such, only 23% of Campylobacter spp. isolates reported via this
surveillance were identified to species level in 2017; 91% of those with species information
recorded were C. jejuni28.
The level of Campylobacter spp. susceptibility testing in 2017 remained low for all antibiotics
included in the surveillance, with the most frequently tested antibiotic being ciprofloxacin (35%).
This low level of susceptibility testing may reflect the fact that the majority of cases do not require
treatment.
The proportion of Campylobacter spp. isolates that were non-susceptible (resistant and
intermediate) increased between 2013 and 2017 for ciprofloxacin (from 42% to 47%) and stayed
low for erythromycin (3%) (Figure 13). A similar pattern was seen for isolates identified to species
level in 2017 with C. jejuni isolates non-susceptible to ciprofloxacin at 44% and 43% in C. coli
isolates, and erythromycin non-susceptibility at 4% in C. jejuni isolates and 12% in C. coli in 2017
(data not shown). The proportion of non-susceptible Campylobacter spp. isolates also increased
between 2013 and 2017 for nalidixic acid (from 45% to 51%) and tetracycline (from 33% to 39%).
C. jejuni C. jejuni
C. coli C. coli
Chapter 3: Antibiotic resistance
26
Figure 13: Percentage susceptibility (interpreted using human EUCAST CBPs; non-susceptible:
resistant and intermediate) in routine laboratory surveillance reports of human Campylobacter spp.
isolates in the UK; 2013 (n=64,764) and 2017 (n=60,408)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
2013 2017 2013 2017 2013 2017 2013 2017
Ciprofloxacin Erythromycin Nalidixic acid Tetracycline
Cam
pylo
bacte
rsp
p.
rep
ort
s
Susceptible Non-susceptible Results not available
3.2.1.5 Control measures in place to reduce risk of transmission
Antibiotic resistant zoonotic organisms present in animals, such as Campylobacter spp., can be
transmitted to humans29. Human Campylobacter infection is often caused by consumption and
handling of raw or undercooked meat, especially poultry meat.
The surveys on retail chicken meat provide evidence that Campylobacter spp. isolates can be
obtained from chicken meat sold at retail in the UK; insufficient data are available to draw
conclusions regarding differences between Campylobacter spp. contamination rates in meat from
different countries of origin. Proportions of isolates with ciprofloxacin and tetracycline resistance
from food were similar to those causing human clinical infection and much higher than the
proportions seen in animals at slaughter. Control measures along the food chain as well as
domestic cooking procedures eliminate or reduce the risk of infection. In the UK, guidance is
provided by the BPC to reduce the prevalence of Campylobacter spp. through different control
measures along the poultry food chain; interventions focus for example on on-farm biosecurity, bird
catching practices, washing practices at the slaughterhouse and packaging30.
The National Health Service (NHS) provides advice on how to prevent Campylobacter poisoning:
“cover and chill raw chicken, don’t wash raw chicken, wash used utensils and cook chicken
thoroughly”; the Food Standards Agency (FSA) adds the advice to wash hands thoroughly with
soap and warm water after handling raw chicken31, 32.
Food poisoning is a notifiable disease in England and Wales according to the Public Health
(Control of Disease) Act 1984g, and Campylobacter spp. as a causative pathogen according to the
Health Protection (Notification) Regulations 2010h. Surveillance of notifications is an important
means to identify and manage situations on campylobacteriosis and other enteric pathogens in
early stages to prevent further spread.
g https://www.legislation.gov.uk/ukpga/1984/22
h http://www.legislation.gov.uk/uksi/2010/659/contents/made
Chapter 3: Antibiotic resistance
27
3.2.1.6 International picture
A full overview for all participating European countries can be found in the EU summary reports on
antibiotic resistance in zoonotic and indicator bacteria from humans, animals and food in 2014–
201633-35. Results below on isolates from animals are interpreted using EUCAST ECOFF values
which means that results are not directly comparable to those based on EUCAST human CBP
values.
The harmonised monitoring of antibiotic resistance in human Campylobacter spp. isolates within
the EU includes testing for susceptibility to ciprofloxacin, erythromycin, gentamicin (invasive
isolates only) and tetracycline36. The same antibiotics are also tested in the EU harmonised
monitoring of resistance in C. jejuni isolated from broiler chickens and turkeys at slaughter.
Compared to the other European MSs, the level of decreased-susceptibility in the UK is generally
lower. The UK was among the EU MSs with the lowest level of decreased-susceptibility to
erythromycin in broiler C. jejuni isolates in 2014 (0%; average for EU MSs: 6%) and 2016 (0.6%;
average for EU MSs: 1.3%). Decreased-susceptibility to ciprofloxacin was also lower than average
in 2014 (44%; average for EU MSs: 70%) and 2016 (41%; average for EU MSs: 67%).
Regarding C. jejuni isolates from turkey, decreased-susceptibility to erythromycin was also lower
than average in 2014 (0.7%; average for EU MSs: 3%), but it was around the average in 2016
(1.1%; average for EU MSs: 1.0%). The level of decreased-susceptibility to ciprofloxacin in turkey
isolates was the lowest of the 10 EU MSs providing data in 2014 (35% vs. 70% on average) and
9 MSs providing data in 2016 (35% vs. 76%).
The UK was one of the three countries reporting the lowest levels of resistance found in C. jejuni
isolated from humans in 2016 to gentamicin, ciprofloxacin, and tetracycline (out of 17 EU MSs),
with erythromycin resistance being lower than the average. Compared with the position in 2013,
the ranking for resistance in human isolates remained similar for all antibiotics tested, the only
exception was for tetracycline where the UK improved, from 6th (out of 14 EU MSs) to 3rd in 201635.
3.2.1.7 Concluding remarks
The data suggest that resistance to erythromycin (one of the antibiotics classed by the WHO as
highest priority critically important antibiotics for human medicine (HP-CIA; see Annex I for detail)
remains (very) low in Campylobacter spp. isolates from broilers and turkeys at slaughter as well as
from human clinical infections, but decreased-susceptibility was detected in around 7% of
Campylobacter spp. isolates from retail chicken meat in 2017.
In line with recent EFSA data on Campylobacter spp. isolates from broiler meat, voluntarily
provided by seven EU MSs, decreased-susceptibility to the HP-CIA ciprofloxacin was common in
Campylobacter spp. isolates from UK retail meat33, 35. Decreased-susceptibility and resistance to
ciprofloxacin is also a concern in C. jejuni isolated from healthy poultry and in human
Campylobacter spp. isolates, where levels of ciprofloxacin resistance continue to be high.
Susceptibility testing on Campylobacter spp. isolates prior to treating with erythromycin or
ciprofloxacin would therefore be recommended, as these antibiotics are two of the treatment
options available (for severe cases).
Chapter 3: Antibiotic resistance
28
3.2.2 Non-typhoidal Salmonella spp.
3.2.2.1 Background
Salmonella are a major cause of foodborne illness in humans and animals. There are more than
2,500 serovars, all of which can cause food poisoning in humans, though fewer than 100 serovars
account for most human infections. Salmonellosis in humans is generally contracted through the
consumption of contaminated animal products, such as eggs, (poultry) meat, and milk37.
Gastrointestinal symptoms caused by Salmonella spp. usually do not require treatment with
antibiotics but severe cases and patients at risk of invasive disease are treated according to
antibiotic susceptibility results (most commonly with ciprofloxacin, azithromycin or 3rd generation
cephalosporins38).
3.2.2.2 Resistance – food-producing animals
Non-typhoidal Salmonella spp. isolates from poultry farms
The results shown in this section from the EU harmonised AMR monitoring scheme for Salmonella
spp. in poultry are from isolates taken from boot swabs, dust samples or composite faecal
samples, collected on broiler chicken, layer chicken and fattening turkey farms under the
framework of the National Control Plans (according to EU Regulations (EC) No 2160/2003i and
No 2073/2005j; see Annex F for more details).
i https://eur-lex.europa.eu/legal-content/EN/ALL/?uri=CELEX:32003R2160 j https://eur-lex.europa.eu/legal-content/EN/ALL/?uri=CELEX%3A32005R2073
Progress on recommendation 2 of the 2015 report –
Sentinel Campylobacter study
“Public health organisations should scope the development of a national sentinel
surveillance system for Campylobacter spp. isolates collected from human infections.
In addition, public health organisations should highlight the importance of identifying
Campylobacter to a species rather than genus level, as different species have different
antibiotic profiles.”
PHE’s Gastrointestinal Bacteria Reference Unit (GBRU) started the process of
routinely collecting human Campylobacter spp. isolates from a selection of laboratories
in England in 2017 in addition to the small number of isolates that are received for
further characterisation during outbreak investigations; with the intention to develop
this into a sentinel surveillance system. The sites chosen are regional specialist PHE
laboratories based in various parts of England. This will enable detailed data collection
on a more representative sample of Campylobacter spp. isolates and allow greater
understanding of AMR trends at species level. The Campylobacter spp. isolates
currently referred to GBRU from these sentinel sites (Leeds, Southampton, Cambridge
and Birmingham) and from two other sites (Oxford and Newcastle) as part of a three-
year FSA funded surveillance project (combined total of 1,914 isolates from all six sites
between January–December 2017), represents a 4% sample of the total number of
cases (n=53,068) which were reported in England in 2017.
Chapter 3: Antibiotic resistance
29
Three (<1%) of 761 Salmonella spp. isolates from poultry farms, sampled in 2014 and 2016, had
detectable resistance to colistin based on EUCAST human CBPs – all three isolates were from
layer farms and isolated in 2014, and none of the 761 isolates were resistant to cefotaxime or
ceftazidime. No or very low (<1%) resistance was detected to ciprofloxacin in broiler, layer or
turkey isolates (Figure 14 and Figure 15).
Figure 14: Percentage resistance (interpreted using EUCAST human CBPs) in Salmonella spp.
obtained from broiler and layer chicken farms in the UK (National Control Plan/EU harmonised
AMR monitoring); 2014 and 201611
%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Resis
tan
t is
ola
tes
Broiler 2014 (n=168) Broiler 2016 (n=170) Layer 2014 (n=58) Layer 2016 (n=34)
Figure 15: Percentage resistance (interpreted using EUCAST human CBPs) in Salmonella spp.
obtained from turkey farms in the UK (National Control Plan/EU harmonised AMR monitoring);
2014 and 201611
%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Resis
tan
t is
ola
tes
2014 (n=162) 2016 (n=169)
Low resistance was observed to nalidixic acid (2%–4%) for broiler and layer isolates, and in turkey
isolates resistance went from 20% in 2014 to 2% in 2016. No Salmonella spp. isolates from broiler
and layer samples showed resistance to meropenem or tigecycline, and resistance to tigecycline in
turkey isolates decreased from 2% to 0% while resistance to gentamicin remained very low (<1%).
Chapter 3: Antibiotic resistance
30
In isolates from broiler farms, a large decrease was detected between 2014 and 2016 in the
proportion of isolates resistant to trimethoprim and gentamicin (Figure 14). Resistance in
Salmonella spp. isolates from layer farms remained low for all antibiotics tested. In Salmonella spp.
isolates from turkey farms, resistance to ampicillin decreased from 23% to 5% and resistance to
trimethoprim from 7% to 2% (Figure 15). In contrast, resistance to tetracycline increased in turkey
isolates (from 49% to 76%) between 2014 and 2016.
Salmonella spp. isolates from broilers and pigs at slaughter
Salmonella spp. isolates from neck skin samples from broilers and isolates from pig carcase swabs
at slaughter were provided by food business operators under the Zoonoses Order 1989k and the
EC Regulation 2073/2005 on microbiological criteria for foodstuff (process hygiene criteria only).
In 2016, 17 Salmonella spp. isolates from broiler neck skin samples were tested for susceptibility,
under the EU harmonised monitoring programme. Based on EUCAST ECOFFs, no decreased-
susceptibility was observed to the HP-CIAs (cefotaxime, ceftazidime, ciprofloxacin and colistin) and
the majority of other antibiotics tested (ampicillin, chloramphenicol, gentamicin, meropenem,
nalidixic acid and tigecycline). Two isolates showed decreased-susceptibility to
sulphamethoxazole, two to trimethoprim and one to tetracycline35.
For pigs, a limited number of isolates were available. Of the nine Salmonella spp. isolates tested in
2015 from samples from healthy pigs, all were susceptible to the HP-CIAs cefotaxime, ceftazidime,
ciprofloxacin and colistin, and to meropenem or tigecycline. Three isolates showed resistance to
ampicillin and three to tetracycline (based on EUCAST human CBPs). In 2017, four Salmonella
spp. isolates were tested, of which all were susceptible to the HP-CIAs cefotaxime, ceftazidime,
ciprofloxacin and colistin. Two isolates were resistant to ampicillin and two to tetracycline.
Resistance in Salmonella Typhimurium isolates
Results on AMR in Salmonella Typhimurium isolates are presented in addition to the data for all
Salmonella spp. since this serovar is also common in humans. Figure 16 shows the resistance
observed in Salmonella Typhimurium isolated from livestock in England and Wales in 2013 and
2017, tested under the clinical surveillance programme (see Annex F for detail).
It should be noted that these isolates were obtained from samples from healthy poultry flocks as
well as samples from clinical cases in cattle, pigs and chickens. In the latter case, samples were
tested for diagnostic purposes, but it is unknown whether these samples were collected pre- or
post-antibiotic treatment, or how many isolations and incidents were represented in the data
included. Therefore, the results may not be representative and should be interpreted with caution.
With regard to HP-CIAs, none of the isolates from cattle, pigs or chickens were resistant to
cefotaxime, ceftazidime, or ciprofloxacin in 2013 and 2017 (Figure 16). Resistance to nalidixic acid
appears to have more than halved (from 6% in 2013 to 2% in 2017). The majority of isolates in
2017 were resistant to ampicillin, chloramphenicol, streptomycin, tetracycline and sulphonamide
compound (73–86%). An apparent increase (from 50% in 2013 to 78% in 2017) in resistance to
chloramphenicol and decrease (from 65% in 2013 to 33% in 2017) in resistance to
trimethoprim/sulphonamide can be seen in Figure 16.
k http://www.legislation.gov.uk/uksi/1989/285/made
Chapter 3: Antibiotic resistance
31
Figure 16: Percentage resistance (interpreted using British Society for Antimicrobial
Chemotherapy (BSAC) human clinical break points where available, indicated with ‡) to selected
antibiotics in Salmonella Typhimurium isolates collected under the clinical surveillance programme
from cattle, pigs and chickens in England and Wales; 2013 and 201710, 39
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Resis
tan
t is
ola
tes
2013 (n=107) 2017 (n=96)
‡ Interpreted using BSAC human CBPs; * Amoxicillin/clavulanate; ** Sulphonamide compound; *** Trimethoprim/
sulphonamide
Most commonly isolated Salmonella serovars
In 2017, serovar Dublin (475 isolates) represented the largest proportion of Salmonella serovars
among isolates recovered from food-producing animals (cattle, pigs, sheep, chickens, turkeys and
ducks) in the UK (both statutory and non-statutory samples), followed by Derby (373 isolates),
Mbandaka (317 isolates), Senftenberg (260 isolates) and Kedougou (211 isolates)40, 41. In 2013 the
top five serovars in England, Wales and Scotland consisted of Dublin (458 isolates), Mbandaka
(294 isolates), Montevideo (248 isolates), Senftenberg (206 isolates) and Kedougou (192 isolates)
(see Annex C for the top ten most isolated serovars from animal samples in 2013 and 2017)40.
3.2.2.3 Resistance – humans
Non-typhoidal Salmonella spp. isolates from human samples
There were 16,911 (non-typhoidal) Salmonella spp. faecal isolates recorded via routine laboratory
surveillance in 2017; susceptibility information was recorded for between 1% (colistin) and 31%
(ciprofloxacin) of isolates (Figure 17). The proportion of Salmonella spp. isolates tested that were
non-susceptible (intermediate and resistant) to HP-CIAs decreased for colistin (from 6% to 3%),
but increased for ciprofloxacin (from 4% to 14%), cefotaxime (from 1% to 2%) and ceftazidime
(from 0% to 4%).
Chapter 3: Antibiotic resistance
32
Figure 17: Percentage susceptible and non-susceptible (intermediate and resistant) isolates
(interpreted using CBPs) in non-typhoidal Salmonella spp. from human faecal isolates (routine
laboratory surveillance reports) in the UK; 2013 (n=7,933) and 2017 (n=16,911)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
2013 2017 2013 2017 2013 2017 2013 2017 2013 2017 2013 2017 2013 2017
Ampicillin Cefotaxime Ceftazidime Chloramphenicol Ciprofloxacin Colistin Gentamicin
Salm
on
ella
sp
p.
rep
ort
s
Susceptible Non-susceptible Results not available
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
2013 2017 2013 2017 2013 2017 2013 2017 2013 2017 2013 2017
Meropenem Nalidixic acid Sulphonamide Tetracycline Tigecycline Trimethoprim
Salm
on
ella
sp
p.
rep
ort
s
With regard to the other antibiotics tested, the proportion of Salmonella isolates that were non-
susceptible increased for chloramphenicol (from 5% to 10%), gentamicin (from 11% to 34%),
nalidixic acid (from 16% to 19%) and tetracycline (from 28% to 35%) between 2013 and 2017
(Figure 17). However, susceptibility testing in routine surveillance remains low (1%–14% in 2013,
1%–31% in 2017).
Resistance in Salmonella Typhimurium isolates
Data on AMR in Salmonella Typhimurium isolated from human faecal specimens are presented in
addition to the data for all Salmonella spp. since this serovar is also common in animals. In both
2013 and 2017, susceptibility patterns from human Salmonella Typhimurium isolates are similar to
those seen in isolates from animals and their environment (Figure 16). Of the isolates tested in
2017 a small proportion was non-susceptible to cefotaxime (4%), ceftazidime (7%) or ciprofloxacin
(10%), and there was no non-susceptibility detected to colistin.
Chapter 3: Antibiotic resistance
33
Figure 18: Percentage resistance (interpreted using CBPs) in S. Typhimurium isolates from
humans reported through routine laboratory surveillance in England and Wales; 2013 (n=1,652)
and 2017 (n=2,424)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
2013 2017 2013 2017 2013 2017 2013 2017 2013 2017 2013 2017 2013 2017
Ampicillin Cefotaxime Ceftazidime Chloramphenicol Ciprofloxacin Colistin Gentamicin
Salm
on
ella
Typ
him
uri
um
re
po
rts
Susceptible Non-susceptible Result not available
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
2013 2017 2013 2017 2013 2017 2013 2017 2013 2017 2013 2017
Meropenem Nalidixic acid Streptomycin Sulphonamide Tetracycline Trimethoprim
Salm
on
ella
Typ
him
uri
um
re
po
rts
With regard to the other antibiotics, a large proportion was non-susceptible to ampicillin (53%),
streptomycin (49%), gentamicin (66%), sulphonamide compound (56%) or tetracycline (63%), see
Figure 18. Reports of susceptibility testing have been consistent between 2013 and 2017, however
they remain low (between 0% and 22% tested for each antibiotic), and as such these results
should be interpreted with caution.
Most commonly isolated non-typhoidal Salmonella serovars
Salmonella Enteritidis and Salmonella Typhimurium continue to be the dominant non-typhoidal
Salmonella serovars identified in gastrointestinal disease reference isolates in the UK in 2017,
representing 27% (n=2,459) and 16% (n=1,423) of referrals, respectively. Compared to the
previous report there were some changes in the top ten identified serovars between 2013 and
2017: the monophasic variant of Salmonella Typhimurium is now listed as the third most frequently
reported serovar in 2017 (7%; in 2013 S. Infantis was third) and Salmonella Montevideo has fallen
from 10th in 2013 to 25th most frequently reported serotype in 2017 (see Annex C).
Chapter 3: Antibiotic resistance
34
3.2.2.4 Control measures in place to reduce risk of transmission
The UK Zoonoses Order 1989 lists the animal species from which Salmonella spp. isolations
should be reported to a Veterinary Investigation Officer of one of the Veterinary Investigation
Centres of APHA40. At a European level, Directive (EC) No. 2003/99l sets out the requirements for
monitoring of zoonoses and zoonotic agents in the EU.
Great Britain also implements National Control Programmes (NCP) for Salmonella in commercial
chicken and turkey sectors. Under the framework of these NCPs, all commercial egg laying
holdings with 350 or more birds, adult breeding flocks with more than 250 birds, all commercial
broiler flocks, breeding turkey holdings with more than 250 adult birds and fattening turkey flocks
with more than 500 birds should be sampled at defined times and intervals (varying by type of bird
(e.g. breeding, laying, meat) and poultry species) by the food business operator or an official
control, taking boot/sock swabs and/or composite faecal or dust samples according to a strict
protocol set out by the respective NCPs and Commission Regulations (e.g. No. 584/2008m for
turkeys). Boot/sock swabs cover the feet of the person sampling, and this person will walk around
the poultry house, making sure to collect material from the floor on the ‘socks’. The protocols
describe how many pairs of swabs should be taken, in which area, and the area covered per
poultry house.
Samples are sent to a government-approved laboratory and subsequently tested for presence of
Salmonella spp. When tested positive for Salmonella, the producer is required to contact the
veterinarian for advice on biosecurity measures to prevent transmission. If the test is positive for
Salmonella Enteritidis or Salmonella Typhimurium, the holding must be cleaned and disinfected,
l https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:32003L0099 m https://eur-lex.europa.eu/legal-content/EN/ALL/?uri=CELEX%3A32008R0584
Salmonella reference laboratory data and genotypic
resistance
In 2017, 9,131 non-typhoidal Salmonella isolates were referred to GBRU, PHE for
confirmation. Whole genome sequencing (WGS) is routinely being used to type non-
typhoidal Salmonella isolates since April 2014. An earlier evaluation of the prediction
of phenotypic resistance from genotypic profiles, in isolates received at GBRU
between April 2014 and March 2015, identified that 98% of the isolates were
concordant, and the largest number of discrepant results were associated with
streptomycin42. WGS has proven to be extremely valuable in rapid screening of
bacterial isolates for emerging resistance mechanisms especially to critical
antibiotics9. Between 2014 and 2017, WGS identified 32 non-typhoidal Salmonella
isolates with transmissible colistin resistance gene mcr-1 (17/32 had history of recent
travel abroad) and one carbapenemase gene blaOXA48 acquired abroad.
APHA is considering validating the Salmonella WGS pipeline to be able to provide
information on presence of AMR genes in relation to the presence of phenotypic
resistance to selected antibiotics. This process is likely to start after the validation of
the serogenotyping platform, which will be ready for implementation in 2020.
Chapter 3: Antibiotic resistance
35
after which an official will take samples of the next flock. If again positive, cleaning and disinfection
will need to be performed again and movement on and off the holding will be restricted.
All Salmonella spp. isolates (except some food and feed isolates) identified in England and Wales
are required to be sent to APHA for serotyping and antibiotic susceptibility testing. The majority of
poultry samples taken in Scotland are sent to APHA and all mammalian samples are tested at
SRUC Consulting Veterinary Services and serotype confirmed at the Scottish Salmonella, Shigella
and Clostridium difficile Reference Laboratory.
As with campylobacteriosis prevention, people are recommended to handle animal products in
food production in a hygienic manner and to ensure that meat is cooked thoroughly. Surveillance of
notifications of food poisoning caused by Salmonella spp. are an important means to identify and
manage situations on salmonellosis in early stages to prevent further spread. Information on local
level incidence of non-typhoidal Salmonella are published routinely (England and Wales only), via
the weekly notification reportsn and (England only) via the Health Protection profile on the
Fingertips Websiteo.
3.2.2.5 International picture
A full overview for all participating European countries can be found in the EU summary reports on
antibiotic resistance in zoonotic and indicator bacteria from humans, animals and food in 2014–
201633-35. Results below on isolates from animals are interpreted using EUCAST ECOFF values,
which may explain some of the discrepancies when compared with results interpreted based on
CBP values.
When comparing the degrees of susceptibility seen in Salmonella spp. isolates from UK broilers
and turkeys in 2014 and 2016 to that of other EU MSs, it can be concluded that the UK is among
the countries with the lowest levels of decreased-susceptibility to HP-CIAs33, 35. No decreased-
susceptibility was detected in isolates from broiler flocks to cefotaxime (0% vs. 0.8% for average of
EU MSs), ceftazidime (0% vs. 0.6% for average of EU MSs) and colistin (0% vs. 2% for average of
EU MSs) and the level of decreased-susceptibility to ciprofloxacin was far below average (9% vs.
54% for average of EU MSs) in 2016.
No decreased-susceptibility was detected in isolates from fattening turkey flocks to cefotaxime (0%
vs. 0.9% for average of EU MSs), ceftazidime (0% vs. 0.2% for average of EU MSs) and colistin
(0% vs. 0.3% for average of EU MSs) and the level of decreased-susceptibility to ciprofloxacin was
far below average (2% vs. 51% for average of EU MSs) in 2016.
In addition, no decreased-susceptibility was detected in isolates from laying hen flocks to
cefotaxime (0% vs. 0.1% for average of EU MSs) and ceftazidime (0% vs. 0% for average of EU
MSs). The level of decreased-susceptibility to colistin (0% vs. 6% for average of EU MSs) and to
ciprofloxacin (9% vs. 17% for average of EU MSs) was below average in 2016.
The UK was also among the countries with the lowest resistance to cefotaxime (0% vs. 1% for
average of EU MSs), ceftazidime (0% vs. 1% for average of EU MSs) and colistin (0% vs. 1% for
average of EU MSs) in Salmonella spp. isolated in 2015 from pigs34.
Resistance in Salmonella spp. isolated from humans in the UK in 2016 showed that the UK was
among the countries with lower than average resistance to HP-CIAs, with the exception of
ceftazidime where the UK has the 18th lowest resistance (out of 21 European MSs)35, 43.
n https://www.gov.uk/government/collections/notifications-of-infectious-diseases-noids
o https://fingertips.phe.org.uk
Chapter 3: Antibiotic resistance
36
Progress on recommendation 1 of the 2015 report
“Public health organisations should work with clinical laboratory colleagues to ensure that all
Salmonella species are sent to the relevant reference laboratories for speciation and
antimicrobial susceptibility testing. The referral form should include data on foreign travel,
including countries visited, in the previous four weeks.”
The additional field on travel has been completed for greater than 50% of non-
typhoidal Salmonella referrals in 2014 and 63% in 2015. In 2016 (January to March),
56% of referrals included information on recent travel, with 48% (831/1,719) of them
indicating no (n=752) or unknown (n=10) recent travel or travel to an unknown
destination (n=69). Of those where travel was indicated (n=888), seven (<1%)
travelled within the UK and an additional 159 (18%) travelled elsewhere in Europe,
406 (46%) travelled to Asia, 163 (18%) travelled to Africa, 118 (13%) to North
America and 24 (3%) to the South Americas. A recent study indicated that there was
no difference in likelihood of non-typhoidal Salmonella bacteraemia (severity)
between those who had travel indication and those who did not44. Further analyses
into the differences in serovars and resistances between travel and non-travel
associated Salmonella are being undertaken.
3.2.2.6 Concluding remarks
The data show low resistance to the majority of the HP-CIAs in Salmonella spp. isolates from food-
producing animals: there was no resistance to colistin or 3rd generation cephalosporins in isolates
obtained from broiler chicken, layer chicken or turkey farms in 2016 or from pig carcase swabs in
2017, and resistance to ciprofloxacin was very low.
In Salmonella spp. from human isolates, resistance to HP-CIAs appears to have increased, which
is of concern when considering treatment options. However, it is hard to draw conclusions from this
given the changes in serovars identified in humans between 2014 and 2017, as well as the change
in susceptibility testing practice over this time. Further analysis by serovar would be beneficial.
In 2016, the highest levels of resistance in isolates from poultry farms were to tetracycline,
especially in turkeys. The highest levels of resistance in human isolates from 2017 were found to
ampicillin, ciprofloxacin and gentamicin. Different Salmonella spp. serovars dominate in the human
and animal populations. Since resistance patterns are related to the Salmonella serovar, this
should be a consideration when comparing general Salmonella spp. data between humans and
animals. For S. Typhimurium, a serovar commonly identified in both animal and human sectors,
susceptibility patterns appear similar between animal isolates and human isolates, with the
exception of lower degrees of susceptibility to chloramphenicol and trimethoprim/sulphonamide in
isolates from animals.
Relative to other European countries, the UK has an average or lower than average resistance to
HP-CIAs in isolates from animals. With regard to human isolates, the UK has lower than average
resistance to HP-CIAs, with the exception of resistance to ceftazidime.
Chapter 3: Antibiotic resistance
37
Progress on recommendation 3 of the 2015 report
"Public health organisations should support the work of professional organisations to
transition UK clinical laboratories to a single standardised nationally agreed methodology for
routine antimicrobial testing in 2016.”
In 2016, the BSAC published support for the EUCAST method, aligning their
breakpoints and withdrawing support for the BSAC methodology45. BSAC also
offered training workshops and support to assist in the transfer of laboratories from
the BSAC to the EUCAST methodp. A review in 2017 found that only 12% of
laboratories were still exclusively using the BSAC methodology for disk diffusion
susceptibility testingq.
3.2.3 Escherichia coli, including ESBL-, AmpC- and carbapenemase-
producers
3.2.3.1 Background
Escherichia coli are frequently found in intestines of humans and animals; mostly as commensals.
Since they harbour and potentially transfer genes conferring antibiotic resistance to other bacteria
in the gut, E. coli are indicator bacteria for antibiotic resistance levels in Gram-negative bacteria
and used for AMR surveillance in humans and food-producing animals. There are many different
strain types and some strains can cause a range of infections, such as urinary and intestinal tract
infections. When localised infections spread to the blood, E. coli bacteraemia (bloodstream
infection) may occur. E. coli was the most common bacterial cause of bloodstream infections in
people in the UK in 2017 which led to the UK Government’s ambition to halve the number of
healthcare-associated Gram-negative bloodstream infections by March 2021.
Extended-spectrum β-lactamase (ESBL-) and AmpC β-lactamase (AmpC-) producing E. coli are of
particular concern since these enzymes convey resistance to a wide range of β-lactam antibiotics,
including penicillins and 3rd generation cephalosporins, and therefore pose a serious therapeutic
challenge to clinicians and veterinarians due to the limited treatment options.
3.2.3.2 Resistance – food-producing animals
Antibiotic susceptibilities were determined for E. coli isolated from caecal samples from healthy
broiler chickens and turkeys at slaughter, collected for the EU harmonised AMR monitoring
scheme in 2014 and 2016 (see Annex F).
No resistance (interpreted using EUCAST human CBPs) was found in E. coli isolates from broilers
to the HP-CIAs cefotaxime, ceftazidime and colistin in 2014 or 2016. A decrease was notable in
resistance to ciprofloxacin (from 4% to 2%). In turkey isolates, a small decrease was notable
between 2014 and 2016 in resistance to ciprofloxacin (from 7% to 5%). Resistance to cefotaxime
and ceftazidime remained very low (<1%); no resistance to colistin was detected (Figure 19).
p http://bsac.org.uk/bsac-to-actively-support-the-eucast-disc-diffusion-method-for-antimicrobial-susceptibility-testing-in-
preference-to-the-current-bsac-disc-diffusion-method/ q https://www.gov.uk/government/publications/uk-smi-report-on-survey-into-susceptibility-testing-methodology/report-on-
survey-into-susceptibility-testing-methodology
Chapter 3: Antibiotic resistance
38
Figure 19: Percentage resistance (interpreted using EUCAST human CBPs) in E. coli isolated
from broiler chickens and turkeys in the UK (EU harmonised monitoring); 2014 and 2016
%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Resis
tan
t is
ola
tes
Broiler 2014 (n=159) Broiler 2016 (n=190) Turkey 2014 (n=168) Turkey 2016 (n=224)
None of the E. coli isolates from broiler chickens showed resistance to meropenem or tigecycline.
Resistance to tetracycline, gentamicin and chloramphenicol showed the largest decrease (from
61% to 44%, 20% to 7% and 13% to 7%, respectively). Resistance to nalidixic acid decreased from
25% to 21%.
None of the isolates from turkey showed resistance to meropenem or tigecycline. The largest
absolute decrease in resistance was for tetracycline (from 79% to 67%), ampicillin (69% to 61%)
and nalidixic acid (from 19% to 14%; Figure 19).
No resistance was observed in the E. coli isolated from caecal samples from healthy pigs to the
HP-CIAs cefotaxime, ceftazidime and colistin, and low resistance was detected to ciprofloxacin
(<2%) in both 2015 and 2017 (Figure 20).
Figure 20: Percentage resistance (interpreted using EUCAST human CBPs) in E. coli isolated
from pigs in the UK (EU harmonised monitoring); 2015 and 2017
%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Resis
tan
t is
ola
tes
2015 (n=150) 2017 (n=186)
Chapter 3: Antibiotic resistance
39
None of the isolates were resistant to meropenem or tigecycline. The highest level of resistance in
E. coli isolates from caecal samples from healthy pigs at slaughter for each year (2015 and 2017)
was to tetracycline (72% in 2015 and 59% in 2017), trimethoprim (49% in 2015 and 36% in 2017)
ampicillin (38% in 2015 and 31% in 2017) and chloramphenicol (32% in 2015 and 23% in 2017),
but decreased for nearly all antibiotics between 2015 and 2017.
The EU harmonised AMR monitoring requires specific testing for presence of ESBL-, AmpC- and
carbapenemase-production in E. coli from pig, broiler and turkey caecal samples at slaughter, as
well as from fresh chicken, pig and bovine meat at retail (see Annex F for methodology).
Carbapenems are not authorised for use in food-producing animal species; however, they are
included to monitor emergence or risk of resistance to those antibiotics in bacteria in man.
Under this selective method, 25% and 22% of the pig samples yielded E. coli resistant to
cefotaxime (1 mg/L) in 2015 and 2017, respectively. For samples from broiler chickens and turkeys
in 2016, this was 30% and 5%, respectively (Table 2). The majority of these resistant isolates had
an ESBL-phenotype and around a third had an AmpC-phenotype. Only a few samples had a
combined ESBL/AmpC- phenotype. None of these E. coli isolates from pigs, broiler chickens and
turkeys were presumptive carbapenemase-producers.
Table 2: ESBL-/AmpC-producing E. coli in pig, broiler chickens and turkey caecal samples at
slaughter following selective culture in the UK; 2015–201734
Pig Broiler chicken Turkey
Species 2015* 2017* 2016* 2016**
No. of samples tested 327 347 382 362
No. of samples yielding E. coli microbiologically resistant to 1mg/L cefotaxime (%)
82 (25) 75 (22) 113 (30) 17 (5)
No. of isolates with ESBL-phenotype (%) 65 (22) 56 (16) 73 (19) 12 (3)
No. of isolates with AmpC-phenotype (%) 21 (7) 23 (7) 40 (10) 5 (1)
No. of isolates with combined ESBL/AmpC-phenotype (%)***
4 (1) 4 (1) 2 (<1) 0
* Data from the UK; ** Data from Great Britain; *** Isolates are also included in the ESBL and AmpC data.
Combined results on resistance in E. coli isolated from cattle, pigs, sheep, chickens and turkeys
from the clinical surveillance programme, where field samples are collected and tested for
diagnostic purposes, are shown in Figure 21. Those samples are tested for diagnostic purposes,
generally isolated from sick animals. In addition, it is unknown whether these samples are collected
pre- or post-antibiotic treatment. Therefore, these results should be interpreted with caution as they
may not be representative of the prevalence in the general population.
In 2017, resistance levels to the HP-CIAs cefotaxime and ceftazidime were similar to those in 2013
(11%/6% in 2013 and 12%/7% in 2017, respectively), whereas a slight decrease was found for
resistance to cefpodoxime (from 6% to 2%) and enrofloxacin (from 8% to 6%). Resistance to
amoxicillin/clavulanate decreased between 2013 and 2017, from 34% to 21%. Other large
decreases from 2013 to 2017 were seen for resistance to florfenicol, neomycin, chloramphenicol,
ampicillin, streptomycin, tetracycline and spectinomycin, but an increase was detected for
resistance to doxycycline (23% to 47%).
Chapter 3: Antibiotic resistance
40
Figure 21: Percentage resistance (interpreted using BSAC breakpoints where available; indicated
by ‡) in E. coli/coliform isolates collected under the clinical surveillance programme from cattle,
pigs, sheep, chickens and turkey in England and Wales; 2013 (n=1,400) and 2017 (n=810)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Resis
tan
t is
ola
tes
2013 2017
‡ Interpreted by BSAC human CBPs; * Amoxicillin/clavulanate; ** Trimethoprim/sulphonamide
Progress on recommendation 7 of the 2015 report
“The Veterinary Medicines Directorate (VMD) will conduct carbapenem resistance monitoring
(as part of the EU monitoring and reporting of antimicrobial resistance in zoonotic and
commensal bacteria in accordance with the EU legislation, Commission Decision
2013/652/EU), a year earlier than mandated.”
Carbapenemases are enzymes that hydrolyse (destroy) carbapenems and other β-
lactam antibiotics, especially in members of the Enterobacteriaceae family. They are
considered an emerging threat worldwide as in many cases carbapenems are the
last effective antibiotic in human medicine against multidrug resistant Gram-negative
bacterial infections. Carbapenems are not used in food-producing animals but
considering the importance in human medicine and the potential dissemination from
humans to animals directly or through environmental routes, resistance to
carbapenems is monitored33.
Monitoring for carbapenemase-producing E. coli commenced in 2015. For 2015,
2016 and 2017, none of the samples collected from broiler chickens, turkey and pigs,
and in parallel none of the samples from pork, beef and broiler meat, yielded
carbapenemase-producing E. coli.
3.2.3.3 Resistance – retail meat
Under the EU harmonised AMR monitoring scheme, meat samples are tested on an agar selecting
for cefotaxime-resistant E. coli, which gives insight into the number of samples potentially showing
ESBL- or AmpC-phenotypes. These phenotypes convey resistance to antibiotics that are important
for treating human infections.
Chapter 3: Antibiotic resistance
41
A total of 312 beef and 312 pork samples were tested in 201546, and 314 beef and 310 pork
samples in 201747. The majority of the tested samples originated from the UK, but a small
proportion originated from other EU countries. Both in 2015 and 2017, two (0.6%) beef samples
yielded E. coli microbiologically resistant to 1mg/L cefotaxime (interpreted using EUCAST
ECOFFs), but in 2017 a smaller proportion of pork samples (0.3%) yielded 1mg/L cefotaxime-
resistant E. coli than in 2015 (2%) (Table 3).
Overall, about 1% of retail beef and pork samples in the UK that were tested in 2015 and 2017
were positive for AmpC- or ESBL-producing E. coli; all positive isolates originated from the UK.
Two of the 2015 isolates (one beef, one pork) and two of the 2017 isolates (one beef, one pork)
had an AmpC-phenotype; the other isolates (2015: one beef, five pork; 2017: one beef) had an
ESBL-phenotype (Table 3).
Two isolates showed decreased-susceptibility to ciprofloxacin; none of the isolates showed
decreased-susceptibility to colistin. All of the isolates were susceptibe to the last resort
carbapenems imipenem, ertapenem, or meropenem (results not shown)46, 47.
Of 313 chicken samples tested in 2016, 141 (45%) yielded E. coli with decreased-susceptibility
(interpreted based on ECOFFs) to 1mg/L cefotaxime48. Of the 141 isolates resistant to 1mg/L
cefotaxime, 93 had an ESBL-phenotype. Forty-eight of the 141 isolates had an AmpC-phenotype
(Table 3).
Table 3: E. coli resistance in retail beef and pork46, 47, and retail chicken48 in the UK; 2015–2017
Beef Pork Chicken
Retail meat 2015 2017 2015 2017 2016
No. of samples tested 312 314 312 310 313
No. of positive samples yielding E. coli microbiologically resistant to 1mg/L cefotaxime (%)
2 (<1) 2 (<1) 6 (2) 1 (<1) 141 (45)
No. of isolates with ESBL-phenotype (%) 1 (<1) 1 (<1) 5 (2) 0 93 (30)
No. of isolates with AmpC-phenotype (%) 1 (<1) 1 (<1) 1 (<1) 1 (<1) 48 (15)
No. of isolates with combined ESBL/AmpC-phenotype (%)*
0 0 0 0 2 (<1)
* These isolates are also included in the ESBL and AmpC data
None of the 141 isolates resistant to 1 mg/L cefotaxime showed decreased-susceptibility to the
carbapenem antibiotics ertapenem, imipenem and meropenem or to colistin. Additionally, none of
the isolates showed decreased-susceptibility to the antibiotics azithromycin, temocillin and
tigecycline. As expected, all isolates had decreased-susceptibility to the β-lactam antibiotic
ampicillin. All of the isolates designated as ESBL-phenotype showed decreased-susceptibility to
the cephalosporin antibiotics cefepime and ceftazidime, and all but one isolate showed decreased-
susceptibility to cefotaxime. All of the isolates designated as AmpC-producers showed decreased-
susceptibility to cefoxitin, cefotaxime and ceftazidime (results not shown)48.
Overall, 30% and 15% of retail chicken samples were positive for ESBL- or AmpC-producing E.
coli respectively. There was a decrease in the proportion of samples positive for ESBL-producing
E. coli compared to a previous (2013–2014) UK study, which reported that 65% of 159 retail
chicken samples were positive for ESBL-producing E. coli49.
3.2.3.4 Resistance – humans
In 2017, 41,891 E. coli bloodstream infections in humans were reported in the UK through routine
laboratory surveillance. The degree of susceptibility testing varied by antibiotic, with those
Chapter 3: Antibiotic resistance
42
recommended for clinical use being tested more frequently and with a higher frequency in
specimens from normally sterile sites.
Since the last One Health report, the level of antibiotic susceptibility testing and non-susceptibility
(intermediate and resistant) of E. coli blood samples has been varied (Figure 22).
Figure 22: Percentage susceptible and non-susceptible* isolates (interpreted using CBPs) in
human E. coli blood isolates in the UK; 2013 (n=35,357) and 2017 (n=41,891)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
2013 2017 2013 2017 2013 2017 2013 2017 2013 2017 2013 2017 2013 2017
Ampicillin Cefotaxime Ceftazidime Chloramphenicol Ciprofloxacin Colistin Gentamicin
E. co
lire
po
rts
Susceptible Non-susceptible Results not available
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
2013 2017 2013 2017 2013 2017 2013 2017 2013 2017 2013 2017
Meropenem Nalidixic acid Sulphonamide Tetracycline Tigecycline Trimethoprim
E. co
lire
po
rts
* Including both resistant and intermediate susceptibility results
The key antibiotics for treatment of Gram-negative infections/bloodstream infections (covered by
the UK Five Year AMR Strategy 2013–20181) presented in Figure 22 indicate that the percentage
non-susceptibility has stayed the same or decreased within the UK between 2013 and 2017. Non-
susceptibility remained moderate in E. coli isolates to ciprofloxacin (20%) and 3rd generation
cephalosporins (cefotaxime and ceftazidime, both 12%) in 2017. Non-susceptibility to colistin was
detected in 1% of isolates tested.
Non-susceptibility also remained very high to ampicillin (63%) and high to trimethoprim (39%),
whereas lower levels of non-susceptibility were recorded for gentamicin (11%) and meropenem
(0%). Some local laboratories undertake selective testing/screening of ESBL presence and record
Chapter 3: Antibiotic resistance
43
this via routine surveillance50. In 2017, 23,402 E. coli urine isolates (2%) were reported as being
tested for ESBL presence, of which 16,452 (70%) yielded ESBLs, a higher proportion as those
tested in 2013 (59%; 5,578/9,532). Eight percent of E. coli blood isolates were tested for ESBL
presence in 2017; of those tested, 40% recorded the presence of an ESBL.
The PHE reference laboratory, AMRHAI, stopped providing a molecular service for detection of
acquired AmpC genes a few years ago. However, similar to the ESBL testing, some local clinical
laboratories do undertake selective testing/screening of AmpC presence and record this via routine
surveillance. In 2017, 5,138 E. coli urine isolates (<1%) were reported as being tested for AmpC
presence, of which 2,002 (38%) yielded AmpC, the same proportion as those tested in 2013 (38%;
485/1,262). Eight percent of E. coli blood isolates were tested for AmpC presence in 2017; of those
tested, 2.5% recorded the presence of an acquired AmpC. The low level of testing for AmpC
suggests limited capacity as well as the high likelihood for selection bias, possibly based on
presence of cephalosporin or carbapenem resistance.
In 2017, the AMRHAI Reference Unit received 3,000 Enterobacteriaceae isolates that were
confirmed positive for at least one carbapenemase, with most of the isolates indicating colonisation
rather than infection13. The ‘big 5’ carbapenemase families (KPC, OXA-48-like, NDM, VIM and
IMP), and combinations thereof, accounted for >99% of isolates. Carbapenemases belonging to
the OXA-48-like family continue to be the most frequently identified, accounting for 48.5% of
confirmed carbapenemase-producing Enterobacteriaceae (CPE) in 2017, followed by NDM
(24.4%), KPC (15.1%), IMP (4.7%) and VIM (2.4%). Since the majority of CPE referred to AMRHAI
in 2017 were from sites suggesting colonisation, minimum inhibitory concentrations (MICs) were
not determined. However, AMRHAI’s MIC data for 700 confirmed CPE isolates indicated that, as in
previous years, CPE isolates were not only resistant to carbapenems but also to multiple other
classes of antibiotics.
3.2.3.5 Control measures in place to reduce risk of transmission
E. coli is commonly found in the lower intestine of humans and livestock. Most strains are harmless
and are opportunistic pathogens whereas some strains, such as Vero cytotoxin-producing E. coli
(VTEC), also known as Shiga toxin-producing E. coli (STEC), can cause serious food-poisoning.
These strains are transmitted to humans through contact with contaminated water and the
environment, and through consumption of contaminated foods (raw or undercooked meat
products). VTEC are destroyed by thoroughly cooking of foods until all parts reach a temperature
of 70oC.
Guidance documents to aid in reducing transmission of, and infection by, VTEC are available from
the UK government website51. Most measures are related to handling, storing and preparing of
food products. In addition, it is important to wash hands thoroughly after using the toilet, handling
raw meat, before meals and after contact with animals. Furthermore, guidance is provided around
farm and petting zoo visits (such as: avoid putting fingers in mouths while on the farm, wash hands
thoroughly, do not eat or drink while touching animals).
Chapter 3: Antibiotic resistance
44
Study on ESBL-producing E. coli in animals, people and food
A recent UK study examined different sources of ESBL-producing E. coli, including
human faeces, sewage, farm slurry, livestock, raw meats, fruit and vegetables in
order to understand the contribution of non-human sources of ESBL-producing E.
coli to the burden of human gut colonisation/infections.
From >20,000 human faeces samples tested, the study estimated that 11% of the
UK population have gut colonisation by ESBL-producing E. coli. Approximately 65%
(n=159) of retail chicken, 3% of pork (n=79) and 1% of beef (n=159) samples, and
28% of farm slurry samples (n=97) were positive for ESBL-producing E. coli, but all
tested fruit and vegetable samples (n=400) were negative49.
Different strains of ESBL-producing E. coli were identified, with ST131 (an
internationally-recognised ‘high-risk’ clone of E. coli) dominant, accounting for over
one-third (35%) of all ESBL-producing E. coli from human faeces and almost a fifth
(18%) of ESBL-producing E. coli from sewage samples. ST131 also dominated
among bloodstream ESBL-producing E. coli included within the study, accounting for
almost two-thirds (64%) of isolates recovered. By contrast, only two (0.9%) livestock
or food ST131 isolates were found in this study (one from chicken meat and one
from a chicken) but both could be distinguished from ST131 from humans.
After excluding ST131, the next E. coli type in rank, overall and in each of the human
sources, was ST38 (9% in sewage isolates, 8% in human faeces and 6% in human
bacteraemia isolates), but no ST38 isolates were found in the meat, slurry or
livestock surveillance isolates, suggesting that it is a ‘human-adapted’ strain.
The dominant ESBLs also differed between sources, with CTX-M-15 most commonly
identified in the human group, accounting for 77% of ESBL- producing E. coli isolates
from human bacteraemia, 71% from human faeces and 54% from sewage, but in
only 7% of isolates from meat and farm slurry. In contrast, CTX-M-1 dominated in
isolates from non-human sources, accounting for 56% of isolates from raw meat,
livestock and farm slurry, but just 5% of ESBL-producing E. coli from blood or human
faeces, and 10% from sewage.
The study showed that most human infections and colonisations with ESBL-
producing E. coli are attributable to a very small number of successful strains
(especially a clone known as ST131), which may be spread from person to person
through poor hygiene or from the environment to individuals in home, community and
healthcare settings. During the study period (2013–14), non-human reservoirs of
ESBL-producing E. coli in the UK had only a limited role in contributing to the major
burden of human disease. Some infected or colonised people may acquire an ESBL-
producing E. coli strain from a non-human source, but evidence from this study
indicates that this is a small minority (<10%).
Chapter 3: Antibiotic resistance
45
In support of the UK Government’s ambitions to reduce healthcare associated Gram-negative
bloodstream infections by 50% by 2021 – with an initial focus on E. coli – PHE, along with
professional and partner organisations, have co-produced resources to help health and social care
economies achieve these reductions by strengthening infection prevention and improved antibiotic
prescribing. Toolkits for the early detection, management and control of CPE have been developed
for acute trusts as well as health and residential settings in the community and initiatives such as
the TARGET antibiotic toolkit, which provides diverse resources to support health professionals
and educate patients in appropriate use of antibiotics, have helped embed stewardship
programmes.
3.2.3.6 International picture
Results below on isolates from animals are interpreted using EUCAST ECOFF values, which
means that results are not directly comparable to those interpreted using CBP values.
The UK is consistently among the EU MSs with the lowest level of decreased-susceptibility to HP-
CIAs in E. coli isolated from broilers and turkeys in 2014 and 201633, 35. In 2016, there was full
susceptibility to cefotaxime, ceftazidime and colistin (average decreased-susceptibility for EU MSs:
4%, 4% and 2%, respectively) and to ciprofloxacin there was decreased-susceptibility in 22%
(average for EU MSs: 64%). In 2015, in comparison to other EU MSs, the UK had the lowest
observed level of decreased-susceptibility to cefotaxime and ceftazidime (0% vs. average of 1% for
EU MSs), lower than average decreased-susceptibility to ciprofloxacin (2% vs. average of 11% for
EU MSs) and only a marginally higher level of decreased-susceptibility to colistin (0.6% vs.
average of 0.4% for EU MSs) in E. coli isolated from pigs34.
With regard to EU harmonised monitoring for presumptive ESBL-/AmpC-/carbapenemase-
producing E. coli, the UK had a lower than average prevalence for ESBL-and AmpC-producing
E. coli isolated from fattening pigs in 2015 (22% and 7% for ESBL- and AmpC-phenotype,
respectively, vs. 32% and 10% on average for EU MSs), from turkeys in 2016 (3% and 1% for
ESBL- and AmpC-phenotype, respectively, vs. 37% and 7% on average for EU MSs) and from
broilers in 2016 (19% and 11% for ESBL- and AmpC-phenotype, respectively, vs. 35% and 24%
on average for EU MSs). The UK also had a lower than average prevalence for ESBL- or AmpC-
producing E. coli isolated from pork samples in 2015 (2% and 0.4% for ESBL- and AmpC-
phenotype, respectively, vs. 7% and 2% on average for EU MSs). Similar results were seen for E.
coli isolates from beef (1% and 1% for ESBL- and AmpC-phenotype, respectively, vs. 5% and 2%
on average for EU MSs) and broiler meat samples (30% and 16% for ESBL- and AmpC-
phenotype, respectively, vs. 36% and 27% on average for EU MSs) in 2016.
The UK data reported to the European Antimicrobial Resistance Surveillance Network (EARS-Net)
showed lower than average resistance in E. coli bacteraemia samples isolated from humans to
fluoroquinolones and 3rd generation cephalosporins but slightly higher resistance to carbapenems
when compared to other EU MSs52.
3.2.3.7 Concluding remarks
Under the EU AMR monitoring scheme, very low levels of resistance were found in broiler and
turkey isolates to 3rd generation cephalosporins (<1%), low resistance to ciprofloxacin (<4% for
broilers and ≤7% for turkeys) and no resistance to colistin. Resistance decreased between 2014
and 2016 to nearly all tested antibiotics in both poultry species. In pig isolates no resistance was
found to 3rd generation cephalosporins or colistin, and low resistance to ciprofloxacin (<2%).
In broilers and pigs, specific testing for ESBL- and AmpC-producing E. coli yielded a high
prevalence (22-30%) with the majority of isolates showing the ESBL-phenotype. In turkeys
Chapter 3: Antibiotic resistance
46
prevalence was around 5%. Prevalence in retail meat was consistently low for pork and beef (<2%)
whereas in chicken meat the prevalence was 45%, with twice as many ESBL-phenotype isolates
being observed than AmpC-phenotype isolates. No carbapenemase-producing E. coli were found
in animal or retail meat samples tested under the EU AMR monitoring scheme during 2015–2017.
E. coli isolates from humans showed high levels of resistance to ampicillin and trimethoprim. The
limited surveillance data available on ESBL-/AmpC-/carbapenemase-producing E. coli in humans,
is largely based on selective testing. Based on data from local laboratories, 38% of E. coli urine
isolates tested showed AmpC presence in 2017, whereas this was 8% for E. coli blood isolates. In
the same year, 40% of E. coli bacteraemia isolates tested showed an ESBL-phenotype. This is
higher than the 8.7% ESBL-positive observed in BSAC UK Bacteraemia Surveillance samples
(n=38/437)r. BSAC tests up to 20 consecutive E. coli bacteraemia isolates each year from
25 centres with good geographical spread throughout the UK and Ireland. The higher proportion of
ESBL-positive isolates observed in the routine surveillance compared to the representative BSAC
sample suggests that testing for presence of ESBLs in E. coli samples is biased in the routinely
reported data towards testing of resistant organisms. A study in England in 2014 indicated that
CTX-M ESBL colonisation was established in the general population and that an estimated 0.1% of
the population were colonised with a CPE53. In 2017 3,000 referred Enterobacteriaceae (primarily
colonisation) isolates were positive for at least one carbapenemase, indicating low prevalence, but
a concerning increase over time.
Progress on recommendation 9 of the 2015 report
“Public and professional One Health activities should be enhanced through
engagement with the European Antimicrobial Awareness Day (EAAD) campaign and
aligning training programmes for human and animal health professionals.”
Infographics, posters, key messages, tweets, articles, and more material were
produced in collaboration with other government departments, the animal industry
and charity organisations for European Antibiotic Awareness Day and subsequently
for World Antibiotic Awareness Week in the past 5 years. This promoted responsible
use of antibiotics in animals, optimal prescribing practice in humans and animals,
best husbandry practices; furthermore, ad hoc surveys were ran and informed the
public on some misunderstood facts. Training material is available for various health
professionals and students; more is being developed for the farming industry.
Engagement during World Antibiotic Awareness Week will continue, to highlight the
importance of tackling antibiotic resistance together.
3.2.4 LA-MRSA
3.2.4.1 Background
The term livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) was coined
following the identification of a novel MRSA lineage in pigs, pig farmers and their families in the
Netherlands and France in the early 2000s. LA-MRSA belonging to multi-locus sequence type
clonal complex 398 (CC398) has subsequently been identified in diverse livestock species (such
r http://www.bsacsurv.org/reports/bacteraemia#results
Chapter 3: Antibiotic resistance
47
as pigs, veal calves, poultry, horses and dairy cows) in Europe and worldwide. In most instances,
LA-MRSA is found in the nose or on the skin of livestock without causing clinical signs of infection.
In humans, LA-MRSA is predominantly identified in those in direct contact with LA-MRSA positive
animals. Such individuals can become colonised, with LA-MRSA being found asymptomatically in
the nose or on the skin. However, as with other types of MRSA such as healthcare- and
community-associated MRSA, if LA-MRSA enters the body through breaches in the skin, it can
cause a local skin infection or, more rarely, invasive disease such as pneumonia or bacteraemia.
LA-MRSA varies widely in their susceptibility to antibiotics, with some displaying resistance to
multiple classes54-57, though various therapeutic options remain available.
3.2.4.2 Resistance – livestock and other animal species
In 2008, a survey was undertaken to determine the prevalence of LA-MRSA positive pig herds in
EU MSs58. Breeding pig holdings in the UK were tested; none of 258 holdings were positive for
CC398 LA-MRSA or for other MRSA.
Subsequently, there have been occasional reports of CC398 LA-MRSA in the UK from livestock
and other animal species. Some have been identified in healthy animals as a result of research/
surveillance studies and others as a result of clinical investigations (Table 4).
Table 4: Published case studies of LA-MRSA from livestock and other animal species in the UK
Origin Animal species
No. positive animals in study
LA-MRSA lineage (MLST-CC)
No. MDR*
Reason for sampling
Year(s) reported References
England Horse 2 CC398 2 Screen (n=1) Clinical (n=1)
2009 59
Poultry 1 CC398 1 Clinical 2013 57, 60
Pig 4 CC398 4 Clinical & research
2014–2017 57, 60, 61
Beef cattle 1 CC398 1 Clinical 2016 57, 60
Northern Ireland
Pig 7 CC398 7 Clinical 2014–2017 60, 62
Pig 3 CC30 0 Clinical 2015 63
Dairy cattle 1 CC398 1 Clinical 2015 60
Scotland Pheasant 1 CC398 1 Clinical 2017 60, 64
UK (Equine hospital)
Horse 12 CC398 11** Research 2017 65
UK (Zoo) Mongoose 3 CC398 3 Clinical & research
2017 66
* Multi-drug resistant; resistant to ≥2 clinically relevant antibiotic classes in addition to β-lactams. All were resistant to
penicillin, oxacillin/cefoxitin and tetracycline; resistance to gentamicin, trimethoprim, erythromycin, clindamycin,
ciprofloxacin ± chloramphenicol was variable; ** Susceptibility data available for 11 isolates; not stated for one isolate.
Associated genomic studies highlight marked genetic diversity indicating multiple independent
incursions rather than expansion of a single CC398 LA-MRSA clone within UK livestock.
To date, all CC398 LA-MRSA from livestock in the UK have been multidrug resistant (MDR;
resistant to 2 antibiotic classes in addition to β-lactams), commonly displaying resistance to
penicillin, oxacillin/cefoxitin, tetracycline, erythromycin, clindamycin and trimethoprim. Genetic
markers associated with resistance to heavy metals (zinc and cadmium) and decreased
susceptibility to biocides were also present in some strains.
Of note, resistance to linezolid has been recorded in two CC398 LA-MRSA isolates from breeding
pigs in Belgium35.
Chapter 3: Antibiotic resistance
48
3.2.4.3 Resistance - retail meat and animal products
In mainland European countries where LA-MRSA is prevalent in food-producing animals, LA-
MRSA has been detected in up to 45% of raw meat samples35. Variable CC398 LA-MRSA rates
have been recorded from raw pork, chicken and turkey meat at retail in the UK (Table 5), with meat
samples originating from the UK and from other European countries.
Table 5: Published reports of LA-MRSA from retail meat and animal products in the UK
Sample type No. samples
No. (%) LA-MRSA positive
Spa type(s)
LA-MRSA lineage (MLST-CC)
No. (%) MDR*
Year study conducted Reference
Raw chicken 30 1 (3) t1939 CC9 1 (100) 2011 55
Raw chicken 50 4 (8) t011, t034, t899
CC398 4 (100) 2015 56
Raw chicken 51 0 - - - 2015 67
Raw turkey 11 2 (18) t011, t034 CC398 1 (50) 2015 56
Raw pork 30 0 - - - 2011 55
Raw pork 63 3 (5) t011, t034 CC398 2 (67) 2015 56
Raw pork 52 2 (4) t011, t034 CC398 2 (100) 2015 67
Raw beef 30 0 - - - 2011 55
Bulk tank milk
~1500 7** (~0.5%)
t011, t2346 CC398 7 (100) 2012 68
* Multi-drug resistant; resistant to ≥2 clinically relevant antibiotic classes in addition to β-lactams. All were resistant to
penicillin, oxacillin/cefoxitin and tetracycline; resistance to trimethoprim, erythromycin, clindamycin ± ciprofloxacin was
variable; ** Recovered from 5 geographically dispersed farms.
A single report of CC9 LA-MRSA (a lineage prevalent in livestock and retail meat in Asia) has been
identified in British chicken meat in the UK. The majority of LA-MRSA recovered from retail meat
was MDR with genomic studies highlighting genotypic diversity, so not indicative of a common
source. One study conducted in the UK reported that the level of LA-MRSA present in the meat
tested was low (<20 CFU/g raw meat)56. CC398 LA-MRSA has also been identified in bulk milk
from dairy cattle in five geographically dispersed farms in the UK68.
3.2.4.4 Resistance - humans
Varying LA-MRSA colonisation rates have been reported among those with occupational exposure
to livestock in mainland Europe, with rates of up to 86% in pig farmers, 37% in poultry farmers,
37% in cattle farmers, 45% in veterinarians and 6% in slaughterhouse workers35.
To date, there have been reports of CC398 LA-MRSA from 13 patients in the UK (Table 6).
Although the context and sampling strategies differed in the various studies, all isolates were from
screening/carriage sites or superficial infections. None reported occupational exposure as a known
risk factor. Most isolates (9; 69%) were MDR. A one-year prospective study of all MRSA recovered
from humans in the East of England highlighted a low LA-MRSA rate; just one of 2,283 (<0.01%)
isolates was identified as CC398 LA-MRSA69.
During 2015/2016, a collaboration between two PHE teams (Healthcare Associated Infections and
Antimicrobial Resistance [HCAI and AMR] and Emerging Infections and Zoonoses [EIZ]) and the
VMD, aimed to estimate the LA-MRSA carriage rate in an “at risk” UK population. The study
screened adult volunteers with frequent occupational or recreational contact with animals,
attending two national Veterinary shows and a Pig and Poultry Fair, for LA-MRSA carriage. The
results will be published shortly.
Chapter 3: Antibiotic resistance
49
Table 6: Reported cases of CC398 LA-MRSA from humans in the UK
Year of isolation Country Specimen type
Spa type Phenotype MDR Reference
2009 Scotland Swab t011 PEN, OXA CIP, TET Yes 70
2010 Scotland Swab t011 PEN, OXA, ERY, CLIND, CIP, TET, GENT
Yes 70
2011 Scotland Swab (umbilicus) t011 PEN, OXA No 70
2011 Scotland Swab t899 PEN, OXA, CLIND, TRIM, TET Yes 70
2011 Scotland Swab (umbilicus) t011 PEN, OXA No 70
2011 Scotland Swab (umbilicus) t899 PEN, OXA, TRIM, TET Yes 70
2010 England Wound swab t011 PEN, OXA, TET No 71
2011 England Wound swab t011 PEN, OXA, FUS, CIP, ERY, CLIND, GENT, TET, TRIM
Yes 71
2011 England Wound swab t011 PEN, OXA, GENT, TET, TRIM Yes 71
2013 England Wound swab t011 PEN, OXA, TET No 72
2013 England Sputum t011 PEN, OXA, CIP, CLIND, ERY, GENT, TET, TRIM
Yes 72
2013 England Sputum t899 PEN, OXA, CIP, ERY, TET, TRIM Yes 72
2013 England Screen swab NS PEN, OXA, ERY, CLIND, TET Yes 69
PEN = penicillin; OXA = oxacillin/cefoxitin; TET = tetracycline; TRIM = trimethoprim; CLIND = clindamycin; ERY =
erythromycin; CIP = ciprofloxacin; FUS = fusidic acid; GENT = gentamicin; MDR = multi-drug resistant; NS = not stated
3.2.4.5 Control measures in place to reduce risk of transmission
The UK government has published two leaflets which provide information and guidance on LA-
MRSA for those who work with livestock or in abattoirs, available at: https://www.gov.uk/
government/publications/la-mrsa-information-for-people-who-work-with-livestock.
The FSA has published a risk assessment of MRSA in the UK food chain with particular focus on
LA-MRSA. FSA advice regarding LA-MRSA was “that raw food should be stored appropriately,
handled hygienically and cooked thoroughly. In combination, these measures should be sufficient
to ensure that any harmful bacteria present are destroyed.”
PHE and its predecessor organisation the Health Protection Agency have issued alerts to improve
awareness of LA-MRSA by diagnostic laboratories73. Sharing of WGS data from UK government
agencies has been initiated to identify possible sources and/or transmission events involving
CC398 LA-MRSA across the One Health landscape.
3.2.4.6 Concluding remarks
Currently, insufficient data are available to establish detailed prevalence of LA-MRSA in the
various domains (e.g. livestock, food, humans) in the UK. Occasional reports of CC398 LA-MRSA
across multiple animal species combined with its detection in the food chain and in humans,
suggest it is present in the different populations; however further monitoring activities will be
needed to establish the extent of its dissemination within and between populations.
Chapter 3: Antibiotic resistance
50
ResAlert – One Health approach to AMR risk management
ResAlert refers to the coordinated UK-wide response to the identification of a resistant
bacterial isolate from an animal, considered to present a high risk for human and/or animal
health. This system was initiated in early 2015. An overview of the four pillars of the
response can be found below. The actions from each pillar do not necessarily take place in
a linear fashion; in particular risk communication, which is a continuous process. The VMD
coordinates the ResAlerts, in collaboration with governmental agencies covering human
and animal health, food safety, and the Devolved Administrations. ResAlerts processed
during 2015–2017 are listed in the table below.
Micro-organism Source (no. of ResAlerts 2015–2017)
Carbapenem-resistant Klebsiella pneumoniae Seal (1)
ESBL-producing E. coli Chicken (1)
LA-MRSA Pig (7); pheasant (1); bovine (1); turkey (1)*
Ciprofloxacin-resistant Salmonella Kentucky Broiler chicken (1); raw pet food (1)
Salmonella Infantis (risk due to persistence) Laying hen (1)
Colistin-resistant Salmonella Typhimurium var
Copenhagen Pig (1)
ESBL-phenotype Salmonella Oslo Horse (1)
* These results differ from Table 4 due to the tables representing a different time period.
Chapter 4: Antibiotics and AMR in the environment
51
Chapter 4: Antibiotics and AMR in the environment
The UK Five Year AMR Strategy 2013–2018 acknowledged the need for more research to
increase understanding of the significance of the different resistance transmission pathways
between the environment, humans and animals1.
There is no structural, statutory surveillance dedicated to assessing the level of AMR in the
environment in the UK. However, the following initiatives provide useful insight into the issue:
The EU Water Framework Directive includes a list of potential water pollutants that must be
carefully monitored in surface waters by the EU MSs to determine the risk they pose to the
aquatic environments. This Watch List of substances includes the macrolides erythromycin,
clarithromycin and azithromycin, the β-lactam amoxicillin and the fluoroquinolone
ciprofloxacin. Monitoring for presence of antibiotics in surface waters will provide valuable
data for future research of AMR in the environment.
In England there is the Reduction and Prevention of Agricultural Diffuse Pollution (England)
Regulations 2018, intended to reduce and prevent the pollution of waters from diffuse
agricultural sourcest. Although this regulation is not specifically intended to reduce AMR
levels in water, this may be a side effect if there is a reduction in pollution of water from
agricultural sources potentially containing antibiotic residues or AMR determinants.
Some of the work performed to increase understanding of antibiotic residues and AMR
determinants in the environment includes the UK Water Industry Research’s (UKWIR)
Chemicals Investigation Programme Phase 2 (CIP2), which runs from 2015 until 2020.
CIP2 samples over 600 UK sewage treatment plants, including samples of river water
upstream and downstream of the plant discharge as well as samples of effluent, covering 74
substances. Preliminary findings of the programme mention that data from CIP2 suggest
some antibiotics found in water are of potential concernu,74.Findings from the first phase of
the CIP showed a high variability in the removal of active pharmaceutical ingredients
between and within plants. Among the substances which were less substantially reduced in
concentration were macrolide antibiotics, which were present in effluents at a higher
concentration than the estimated ‘predicted no effect concentrations’.
Phase 3 of CIP is now being planned and will focus on various aspects of AMR across water
treatment works following on from the previous phases.
In terms of future work, in 2018 a network comprising 23 partners (including the UK Government
agencies APHA, Cefas, Environment Agency, PHE and VMD) from 15 countries (including Low
and Middle Income Countries) was awarded funding from the Joint Programming Initiative on AMR.
The network aims to identify robust, measurable surveillance indicators and methodologies for
assessing environmental AMR levelsv.
As part of the next UK AMR National Action Plan, developing an improved evidence base on AMR
in the environment will be an area of importance for the UK over the next five years.
s https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A32018D0840
t http://www.legislation.gov.uk/uksi/2018/151/contents/made
u https://ukwir.org/the-chemicals-investigation-programme-phase-2,-2015-2020
v https://www.jpiamr.eu/supportedprojects/7th-call-results/
Chapter 5: Discussion
52
Chapter 5: Discussion The One Health Report presents data on antibiotic use in human and veterinary medicine, and on
antibiotic resistance in key pathogens isolated from food-producing animals, retail meat and
humans, with a view to assess the occurrence of resistance along the food chain. In addition, it
adds context to the presented surveillance data by providing information on control measures in
place to reduce the risk of transmission of the bacteria monitored and policy decisions that have
been taken to tackle AMR.
The report shows that substantial reductions have been achieved in antibiotic use in 2017 across
the animal and human sector since the publication of the first UK One Health Report in 2013, with
35% reduction in total sales (in tonnes) of antibiotics for use in animals (in food-producing animals,
the reduction in mg/kg is 40%), and 6% reduction in antibiotics prescribed in human medicine.
The reductions in the animal sector highlight how the food-producing animal sectors, including
producers, their representative bodies and veterinarians, have taken robust action to address the
threat of AMR. Actions have included improvements with regard to animal health and welfare
plans, focusing on disease prevention (e.g. through vaccination), biosecurity, husbandry, cleaning
and disinfection, nutrition and promoting responsible antibiotic use. In addition, animal livestock
sectors have shown willingness to accept change, seek innovation and share best practice. In
addition, several animal sectors (e.g. cattle, sheep, meat poultry, laying hens, pigs) have
voluntarily banned or severely limited the use of HP-CIAs10.
In the human sector, the reduction in antibiotic use reflects improved focus on antibiotic
stewardship activities and the impact of national quality improvement schemes, as well as
professional training and public engagement.
Since the publication of the previous One Health Report, a lot of activities have taken place under
the umbrella of the One Health approach. There is continuing close collaboration between the
animal and human health domains, for example through research into ESBL-producing E. coli in
animals, humans and food (see text box on p.44), the response to the discovery of mcr-1-mediated
colistin resistance (see text box on p.9), and the coordinated UK-wide response to the identification
of resistant bacterial isolates from animals considered to present a high risk for human and/or
animal health (ResAlert; see text box on p.50). In addition, harmonised surveillance indicators
developed by ECDC, EFSA and EMA have been used for this report, showing progress in reducing
antibiotic use and AMR in both food-producing animals and people.
The previous years have also seen joint presentations at conferences and shared workshops on
antibiotic use and resistance. Cross-government agencies continued to be actively involved in
promoting antibiotic stewardship across domains, for example through the Antibiotic Guardian
campaign and coordinated actions to raise awareness during European Antibiotic Awareness Day
and World Antibiotic Awareness Week (see text box on p.19). Governmental organisations from
both the animal and human domains are involved in international work, for example through the
One Health European Joint Programme, the Joint Programming Initiative on AMR and the Fleming
Fund.
However, there is also room for improvement and further enhancements to the One Health
approach in order to tackle the issue of AMR. The UK AMR Strategy 2013–2018 included as one
of the key areas for future action in its UK Commitment to Action “better access to and use of
surveillance data in human and animal sectors through new arrangements that facilitate greater
consistency and standardisation of the data collected across the system and encourage improved
data linkage”. Despite efforts to harmonise and standardise methodology across domains, this has
not happened to the extent needed to draw relevant conclusions from the data currently available.
Chapter 5: Discussion
53
Recording of data that allow comparison is recommended, in addition to identifying drug-bug
combinations of importance to both veterinary and human medicine.
Harmonisation is lacking in various ways. For example, laboratory methodologies vary between UK
countries and domains, data on AMR are not routinely collected across different sectors (for
example, currently there are no routine surveillance data available on Salmonella spp. and
Campylobacter spp. in retail meat, nor is routine surveillance implemented on AMR in the
environment), and the panel of antibiotics for which resistance is tested differs between isolates
obtained from animals, humans and food. Improved integration of surveillance on AMR should take
place at all levels and cover not only data collection but also data analysis, interpretation and
reporting of results. Communication between the various organisations involved in the UK
surveillance on antibiotic use and resistance (such as government departments, laboratories,
competent authorities) needs to be further strengthened.
As highlighted above, data on AMR included in this report are not fully comparable across
domains, mainly due to differences in methodologies used for assessing susceptibility to
antibiotics. It is clear though that the level of bacterial resistance has reduced between 2013 and
2017 for the majority of antibiotics tested in bacteria from healthy food-producing animals at
slaughter. The level of decreased antibiotic susceptibility in bacterial isolates obtained from meat at
retail appears higher than the levels reported in animals at slaughter. This may indicate that cross-
contamination occurs during processing of meat, leading to greater resistance prevalence and
highlighting the importance of campaigns on safe food preparation both at home and in
restaurants.
The data included in this report show that the level of antibiotic use in food-producing animals and
humans has decreased over recent years. The decrease in the levels of resistance in bacterial
isolates obtained from healthy animals at slaughter coincides with the decrease of antibiotic use,
while antibiotic resistance in human medicine has remained generally stable. A systems map was
developed by DHSC and Defra, outlining the links between the various domains and highlighting
the complexities behind AMR (Figure 23). The lack of harmonisation and integration across
systems hampers the understanding of the complexity of AMR and the factors influencing the
development and spread of resistance. More work is needed to improve the understanding of the
relative contribution of the different sectors as well as the routes and pathways to the development,
transmission and persistence of resistance within and between domains. This would enable the
development of evidence-based targeted interventions aiming at tackling the issue of AMR as part
of a One Health approach.
Data quality needs to be improved in all sectors, for example in terms of coverage, granularity and
validation. Future One Health Reports should seek to include estimates on the number of people
and animals treated each year. To obtain these estimates, more insight would be needed into
dosing and treatment duration, which would need to come from animal/patient-level prescription
data. Preferably, integrated, meaningful indicators to monitor progress on AMR and antibiotic use
across domains should be developed. Ideally, future One Health Reports should also include data
on antibiotic use and resistance in companion animals and horses. It should be explored what data
are available on antibiotic use in companion animals and horses and whether a standardised
national denominator could be established so that data from companion animals and horses could
be analysed to the same level as data from food-producing animals.
The need for including data on AMR from a wider range of bacteria (such as bacteria included in
the WHO priority list that are of relevance to animal health) should also be explored. Joint horizon
scanning and response to emerging risks from AMR should be a continuous process to review and
revise the surveillance needs across domains. New tools and methodologies (such as whole
Chapter 5: Discussion
54
genome sequencing) are becoming increasingly available, which will add to the knowledge base as
they provide new insights into resistance, resistance relatedness and provenance, and resistance
mechanisms.
The years following the publication of the UK Five Year AMR Strategy 2013–20181 have provided
a preview of what can be achieved when a cross-government One Health approach is applied in
the fight against AMR. This work needs to be continued and further expanded, and the One Health
approach needs to be further strengthened, specifically by connecting environment, food, animals
and humans with contributions from the different government departments, as well as counterparts
from the Devolved Administrations to work together in the fight against AMR. In January 2019, the
UK Government published a new five-year National Action Plan to tackle AMR75 alongside its
twenty-year Vision in which AMR is contained and controlled by 204076. Building on the
considerable achievements made during the previous UK AMR Strategy, the plan sets out
challenging ambitions and actions for the next five-years taking a One Health approach for
delivery.
In order to combat AMR appropriately and effectively, concerted collaborative efforts are necessary
across the human health, veterinary medicine, food and environment sectors. A truly One Health
approach must involve partnerships between those working at the interface of multiple related
disciplines and will be crucial to ensuring a robust response to the threat of AMR at local, regional
and global level. These approaches will bring future improvements and actions that will result in
further progress against the threat of antimicrobial resistance.
Figure 23: AMR systems map: influences on the development of AMR at top level, taken from
‘Antimicrobial Resistance (AMR) Systems Map Overview of the factors influencing the
development of AMR and the interactions between them’77
References
55
References 1. Department of Health and Social Care, Department for Environment Food & Rural Affairs. UK Five Year Antimicrobial Resistance Strategy 2013 to 2018, 2013. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/244058/20130902_UK_5_year_AMR_strategy.pdf.
2. The Review on Antimicrobial Resistance. Tackling drug-resistant infections globally: final report and recommendations, 2016. Available from: https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf.
3. European Commission. A European One Health Action Plan against Antimicrobial Resistance (AMR), 2017. Available from: https://ec.europa.eu/health/amr/sites/amr/files/amr_action_plan_2017_en.pdf.
4. European Medicines Agency. Updated advice on the use of colistin products in animals within the European Union: development of resistance and possible impact on human and animal health, 2016. EMA/CVMP/CHMP/231573/2016. Available from: https://www.ema.europa.eu/documents/scientific-guideline/updated-advice-use-colistin-products-animals-within-european-union-development-resistance-possible_en-0.pdf.
5. European Medicines Agency. Answers to the requests for scientific advice on the impact on public health and animal health of the use of antibiotics in animals, 2014. EMA/381884/2014. Available from: https://www.ema.europa.eu/documents/other/answers-requests-scientific-advice-impact-public-health-animal-health-use-antibiotics-animals_en.pdf.
6. Public Health England. UK One Health Report - Joint report on human and animal antibiotic use, sales and resistance, 2013, 2015. 2015160. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/447319/One_Health_Report_July2015.pdf.
7. Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, et al. Emergence of plasmid-mediated colistin resistance mechanism mcr-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infectious Diseases. 2016;16(2):161-8.
8. Randall LP, Horton RA, Lemma F, Martelli F, Duggett NAD, Smith RP, et al. Longitudinal study on the occurrence in pigs of colistin resistant E. coli carrying mcr-1 following the cessation of use of colistin. Journal of Applied Microbiology. 2018;doi: 10.1111/jam.13907.
9. Doumith M, Godbole G, Ashton P, Larkin L, Dallman T, Day M, et al. Detection of the plasmid-mediated mcr-1 gene conferring colistin resistance in human and food isolates of Salmonella enterica and Escherichia coli in England and Wales. Journal of Antimicrobial Chemotherapy. 2016;71(8):2300-5.
10. UK-VARSS. UK Veterinary Antibiotic Resistance and Sales Surveillance Report (UK-VARSS 2017), 2018. New Haw, Addlestone: Veterinary Medicines Directorate. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/750811/_1473963-v1-UK-VARSS_2017_Report_FINAL.pdf.
11. UK-VARSS. UK Veterinary Antibiotic Resistance and Sales Surveillance Report (UK-VARSS 2016), 2017. New Haw, Addlestone: Veterinary Medicines Directorate. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/707974/_1274590-v2-VARSS_2016_for_GOV.pdf.
12. British Poultry Council. Antibiotic Stewardship - Report 2018, 2018. Available from: https://www.britishpoultry.org.uk/bpc-antibiotic-stewardship-report-2018/#anchor.
13. Public Health England. English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR) - Report 2017, 2017. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/656611/ESPAUR_report_2017.pdf.
14. Public Health Wales. A Report from Public Health Wales Healthcare Associated Infection, Antimicrobial Resistance & Prescribing Programme (HARP team) - Antibacterial Usage in Primary Care In Wales 2013/14 - 2017/18, 2018. Available from: http://www.wales.nhs.uk/sitesplus/documents/888/Antibacterial%20Usage%20in%20Primary%20Care%20in%20Wales%202013-2017%20%28financial%20years%29.pdf.
References
56
15. HSC Public Health Agency. Surveillance of Antimicrobial Use and Resistance in Northern Ireland, Annual Report, 2017, 2017. Available from: http://www.publichealth.hscni.net/sites/default/files/AMR_annual_report_final_0.pdf.
16. Health Protection Scotland. Scottish One Health Antimicrobial Use and Antimicrobial Resistance Report 2016, 2017. Available from: https://www.hps.scot.nhs.uk/haiic/amr/resourcedetail.aspx?id=3378.
17. European Medicines Agency. European Surveillance of Veterinary Antimicrobial Consumption. Sales of veterinary antimicrobial agents in 30 European countries in 2016, 2018. EMA/184855/2017. Available from: https://www.ema.europa.eu/documents/report/sales-veterinary-antimicrobial-agents-30-european-countries-2016-trends-2010-2016-eighth-esvac_en.pdf.
18. European Centre for Disease Prevention and Control. Summary of the latest data on antibiotic consumption in the European Union - ESAC-Net surveillance data, 2017. Available from: https://ecdc.europa.eu/sites/portal/files/documents/Final_2017_EAAD_ESAC-Net_Summary-edited%20-%20FINALwith%20erratum.pdf.
19. European Medicines Agency. Guidance on collection and provision of national data on antimicrobial use by animal species/categories, 2018. EMA/489035/2016. Available from: https://www.ema.europa.eu/documents/scientific-guideline/guidance-collection-provision-national-data-antimicrobial-use-animal-species/categories_en.pdf.
20. European Centre for Disease Prevention and Control, European Food Safety Authority Panel on Biological Hazards, European Medicines Agency Committee for Medicinal Products for Veterinary Use. ECDC, EFSA and EMA Joint Scientific Opinion on a list of outcome indicators as regards surveillance of antimicrobial resistance and antimicrobial consumption in humans and food-producing animals. EFSA Journal. 2017;15(10):5017.
21. Food Standards Agency. Campylobacter, 2018. Available from: https://www.food.gov.uk/safety-hygiene/campylobacter.
22. Public Health England. Summary of antimicrobial prescribing guidance – managing common infections. PHE context, references and rationales for Clinical Commissioning Groups, Commissioning Support Units and Primary Care Providers, 2018. 2018511. Available from: https://www.gov.uk/government/publications/managing-common-infections-guidance-for-primary-care.
23. Task Force on Zoonoses Data Collection. Report of the Task Force on Zoonoses Data Collection including a proposal for a harmonized monitoring scheme of antimicrobial resistance in Salmonella in fowl (Gallus gallus), turkeys, and pigs and Campylobacter jejuni and C. coli in broilers. EFSA Journal. 2007;96:1-46.
24. Public Health England. FSA Project FS241044 Antibiotic Resistance Report for FS241044 - Sept 2016 (Final), 2016. Available from: https://www.food.gov.uk/sites/default/files/media/document/fs241044finreport.pdf.
25. Thwaites RT, Frost JA. Drug resistance in Campylobacter jejuni, C. coli, and C. lari isolated from humans in north west England and Wales, 1997. Journal of Clinical Pathology. 1999;52(11):812-4.
26. Public Health England. FSA Project FS102121 - Antimicrobial resistance in Campylobacter jejuni and Campylobacter coli from retail chilled chicken in the UK (Year 2: 2015-16), 2017. Available from: https://www.food.gov.uk/sites/default/files/media/document/fs102121y2report.pdf.
27. Willis C, Jorgensen F, Elviss N, Cawthraw S, Randall L, Ellington M, et al. Final report - FSA Project FS101196: Surveillance Study of Antimicrobial Resistance in Bacteria Isolated from Chicken and Pork Sampled on Retail Sale in the United Kingdom, 2018. Available from: https://www.food.gov.uk/research/foodborne-diseases/surveillance-study-of-antimicrobial-resistance-in-uk-retail-chicken-and-pork#research-report.
28. Public Health England. UK Standards for Microbiology Investigations. Identification of Campylobacter species. Bacteriology – Identification. 2018;ID 23(3.1):1-24.
29. World Health Organization. Fact Sheet - Campylobacter, 2018. Available from: https://www.who.int/news-room/fact-sheets/detail/campylobacter.
30. British Poultry Council. A Guide to Interventions, Available from: https://www.britishpoultry.org.uk/a-guide-to-interventions/.
31. Food Standards Agency. Campylobacter levels remain steady, Available from: https://www.food.gov.uk/news-alerts/news/campylobacter-levels-remain-steady.
References
57
32. National Health Service. Why you should never wash raw chicken, Available from: https://www.nhs.uk/live-well/eat-well/never-wash-raw-chicken/.
33. European Food Safety Authority, European Centre for Disease Prevention and Control. The European Union summary report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2014. EFSA Journal. 2016;14(2):4380 (207 pp.).
34. European Food Safety Authority, European Centre for Disease Prevention and Control. The European Union summary report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2015. EFSA Journal. 2017;15(2):4694 (212 pp.).
35. European Food Safety Authority, European Centre for Disease Prevention and Control. The European Union summary report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2016. EFSA Journal. 2018;16(2):5182 (270 pp.).
36. European Centre for Disease Prevention and Control. EU protocol for harmonised monitoring of antimicrobial resistance in human Salmonella and Campylobacter isolates – June 2016, 2016. ISBN 978-92-9193-890-2. Available from: http://ecdc.europa.eu/sites/portal/files/media/en/publications/Publications/antimicrobial-resistance-Salmonella-Campylobacter-harmonised-monitoring.pdf.
37. Public Health England. Salmonella data 2006 to 2015 - National laboratory data for residents of England and Wales, 2016. 22016581. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/598401/Salmonella_2016_Data.pdf.
38. National Institute for Health and Care Excellence (NICE). British National Formulary - Gastro-intestinal system infections, antibacterial therapy. Available from: https://bnf.nice.org.uk/treatment-summary/gastro-intestinal-system-infections-antibacterial-therapy.html.
39. UK-VARSS. UK Veterinary Antibiotic Resistance and Sales Surveillance Report (UK-VARSS 2013), 2014. New Haw, Addlestone: Veterinary Medicines Directorate. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/440744/VARSS.pdf.
40. Animal & Plant Health Agency. Salmonella in livestock production in Great Britain, 2017, 2018. ISBN 1 8995 1350 7. Available from: https://www.gov.uk/government/publications/salmonella-in-livestock-production-in-great-britain-2017.
41. UK-VARSS. Supplementary Material (UK-VARSS 2017), 2018. New Haw, Addlestone: Veterinary Medicines Directorate. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/750933/_1473965-v2-UK-VARSS_2017_Supplementary_Material_FINAL.pdf.
42. Neuert S, Nair S, Day M, Doumith M, Ashton P, Mellor K, et al. Prediction of Phenotypic Antimicrobial Resistance Profiles From Whole Genome Sequences of Non-typhoidal Salmonella enterica. Frontiers in Microbiology. 2018;doi: 10.3389/fmicb.2018.00592.
43. European Food Safety Authority, European Centre for Disease Prevention and Control. EU Summary Report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2013. EFSA Journal. 2015;13(2):4036 (178 pp.).
44. Katiyo S, Muller-Pebody B, Minaji M, Powell D, Johnson A, De Pinna E, et al. The Epidemiology and Outcomes of Non-Typhoidal Salmonella Bacteraemias from England, 2004 to 2015. Journal of Clinical Microbiology. 2018;doi:10.1128/JCM.01189-18.
45. Brown D, Wootton M, Howe R. Antimicrobial susceptibility testing breakpoints and methods from BSAC to EUCAST. Journal of Antimicrobial Chemotherapy. 2016;doi:10.1093/jac/dkv287.
46. Animal & Plant Health Agency. FINAL REPORT - FS102109 - EU Harmonised Surveillance of Antimicrobial Resistance (AMR) in Bacteria from Retail Meats (Year 1), 2016. Available from: https://www.food.gov.uk/sites/default/files/media/document/fs102109finreport.pdf.
47. Animal & Plant Health Agency. FINAL REPORT - FS102109 - EU Harmonised Surveillance of Antimicrobial Resistance (AMR) in Bacteria from Retail Meats (Year 3 - Beef and Pork, 2017), 2018. Available from: https://www.food.gov.uk/sites/default/files/media/document/fs102109-year3_0.pdf.
48. Animal & Plant Health Agency. FINAL REPORT - RDFS102109 - EU Harmonised Surveillance of Antimicrobial Resistance (AMR) in E. coli from Retail Meats (Year 2 - Chicken), 2017. Available from: https://www.food.gov.uk/sites/default/files/media/document/fs102109y2.pdf.
References
58
49. Randall LP, Lodge MP, Elviss NC, Lemma FL, Hopkins KL, Teale CJ, et al. Evaluation of meat, fruit and vegetables from retail stores in five United Kingdom regions as sources of extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant Escherichia coli. International Journal of Food Microbiology. 2017;241:283-90.
50. Standards Unit Public Health England. UK Standards for Microbiology Investigations - Detection of Enterobacteriaceae producing extended spectrum β-lactamases. Bacteriology. 2016;B59(4.1):31.
51. Public Health England. Guidance - Shiga toxin-producing Escherichia coli (STEC): symptoms, how to avoid, how to treat, 2017. Available from: https://www.gov.uk/government/publications/vero-cytotoxin-producing-escherichia-coli-symptoms-how-to-avoid-how-to-treat/vero-cytotoxin-producing-escherichia-coli-symptoms-how-to-avoid-how-to-treat.
52. European Centre for Disease Prevention and Control. Annual Epidemiological Report for 2017 - Antimicrobial consumption, 2018. ISBN 978-92-9498-099-1. Available from: https://ecdc.europa.eu/sites/portal/files/documents/ESAC-NET-reportAER-2017-updated.pdf.
53. McNulty C, Lecky D, Xu-McCrae L, Nakiboneka-Ssenabulya D, Chung K-T, Nichols T, et al. CTX-M ESBL-producing Enterobacteriaceae: estimated prevalence in adults in England in 2014. Journal of Antimicrobial Chemotherapy. 2018;73(5):1368-88.
54. Butaye P, Argudín MA, Smith TC. Livestock-associated MRSA and its current evolution. Current Clinical Microbiology Reports. 2016;3:19-31.
55. Dhup V, Kearns A, Pichon B, Foster HA. First report of identification of Livestock-Associated MRSA ST9 in retail meat in England. Epidemiology and Infection. 2015;143:2989-92.
56. Fox A, Pichon B, Wilkinson H, Doumith M, Hill RL, McLauchlin J, et al. Detection and molecular characterization of Livestock-Associated MRSA in raw meat on retail sale in North West England. Letters in Applied Microbiology. 2017;64(3):239-45.
57. Sharma M, Nunez-Garcia J, Kearns AM, Doumith M, Butaye P, Argudín MA, et al. Livestock-associated methicillin resistant Staphylococcus aureus (LA-MRSA) CC398 isolated from UK animals belong to European lineages. Frontiers in Microbiology. 2016;7:1741.
58. European Food Safety Authority. Analysis of the baseline survey on the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in holdings with breeding pigs, in the EU, 2008 - Part A: MRSA prevalence estimates. EFSA Journal. 2009;7(11):1376.
59. Loeffler A, Kearns AM, Ellington MJ, Smith LJ, Unt VE, Lindsay JA, et al. First isolation of MRSA ST398 from UK animals: a new challenge for infection control teams? Journal of Hospital Infections. 2009;72:269-71.
60. Anonymous. Antimicrobial resistance update: LA-MRSA. Veterinary Record. 2017;181(13):340.
61. Hall S, Kearns A, Eckford S. Livestock Associated MRSA detected in pigs in GB. Veterinary Record. 2015;176(6):151-2.
62. Hartley H, Watson C, Nugent P, Beggs N, Dickson E, Kearns A. Confirmation of LA-MRSA in pigs in the UK. Veterinary Record. 2014;175(74-75).
63. Lahuerta-Marin A, Guelbenzu-Gonzalo M, Pichon B, Allen A, Doumith M, Lavery JF, et al. First report of lukM-positive livestock-associated methicillin-resistant Staphylococcus aureus CC30 from fattening pigs in Northern Ireland. Veterinary Microbiology. 2016;182:131-4.
64. Sharma M, AbuOun M, Nunez-Garcia J, Rogers J, Welchman D, Teale C, et al. MRSA spa type t899 from food animals in the UK. Veterinary Record. 2018;182:697-8.
65. Bortolami A, Williams NJ, McGowan CM, Kelly PG, Archer DC, Corrò M, et al. Environmental surveillance identifies multiple introductions of MRSA CC398 in an equine veterinary hospital in the UK, 2011-2016. Scientific Reports. 2017;7:5499.
66. Bortolami A, Verin R, Chantrey J, Corrò M, Ashpole I, Lopez J, et al. Characterization of Livestock-Associated Methicillin Resistant Staphylococcus aureus CC398 and mecC-positive CC130 from Zoo Animals in the United Kingdom. Microbial Drug Resistance. 2017;23:908-14.
67. Hadjirin NF, Lay EM, Paterson GK, Harrison EM, Peacock SJ, Parkhill J, et al. Detection of livestock-associated meticillin-resistant Staphylococcus aureus CC398 in retail pork, United Kingdom. Eurosurveillance. 2015;20(24):21156.
References
59
68. Paterson GK, Larsen J, Harrison EM, Larsen AR, Morgan FJ, Peacock SJ, et al. First detection of livestock-associated methicillin-resistant Staphylococcus aureus CC398 in bulk tank milk in the United Kingdom, January to July 2012. Eurosurveillance. 2012;17(50):20337.
69. Harrison EM, Coll F, Toleman MS, Blane B, Brown NM, Török ME, et al. Genomic surveillance reveals low prevalence of livestock associated methicillin-resistant Staphylococcus aureus in the East of England. Scientific Reports. 2017;7(1):7406.
70. Ward MJ, Gibbons CL, McAdam PR, Van Bunnik BAD, Girvan EK, Edwards GF, et al. Time-Scaled Evolutionary Analysis of the Transmission and Antibiotic Resistance Dynamics of Staphylococcus aureus Clonal Complex 398. Applied and Environmental Microbiology. 2014;80:7275-82.
71. Pichon B, Vickers A, Pike R, Hill R, Harwin L, Cookson B, et al. Characterisation of Staphylococcus aureus belonging to CC398 from humans in England. International Symposium on Staphylococci and Staphylococcal Infections, August 2012, Lyon, France. 2012. Available from: https://alere-technologies.com/fileadmin/Media/Paper/Poster/16-305-cc398_in_UK.pdf.
72. Kinross P, Petersen A, Skov R, Van Hauwermeiren E, Laurent F, Voss A, et al. Livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) among MRSA from humans, EU/EEA countries, 2013. Eurosurveillance. 2017;22(44):16-00696.
73. Health Protection Agency. HPA reiterates need for vigilance on Community MRSA. Health Protection Report. 2008;2(25).
74. Comber S, Gardner M, Sörme P, Leverett D, Ellor B. Active pharmaceutical ingredients entering the aquatic environment from wastewater treatment works: A cause for concern? Science of the Total Environment. 2018;613-614:538-47.
75. HM Government. Tackling antimicrobial resistance 2019–2024 - The UK’s five-year national action plan, 2019. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/773130/uk-amr-5-year-national-action-plan.pdf.
76. HM Government. Contained and controlled - The UK’s 20-year vision for antimicrobial resistance 2019. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/773065/uk-20-year-vision-for-antimicrobial-resistance.pdf.
77. Department of Health and Social Care, Department for Environment Food & Rural Affairs. Antimicrobial Resistance (AMR) Systems Map - Overview of the factors influencing the development of AMR and the interactions between them, 2014. Available from: https://www.gov.uk/government/publications/antimicrobial-resistance-amr-systems-map.
78. Public Health England. Laboratory reporting to Public Health England - A guide for diagnostic laboratories, 2016. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/739854/PHE_Laboratory_Reporting_Guidelines.pdf.
79. Walpole SC, Prieto-Merino D, Edwards P, Cleland J, Stevens G, Roberts I. The weight of nations: an estimation of adult human biomass. BMC Public Health. 2012;12(1):439.
80. World Health Organization. Critically Important Antimicrobials for Human Medicine: 5th Rev, 2017. Available from: https://www.who.int/foodsafety/publications/antimicrobials-fifth/en/.
81. Budd E, Sharland M, Hand K, Howard P, Wilson P, Wilcox M, et al. Adaptation of the WHO essential medicines list for national antibiotic stewardship policy. ECCMID 2018 poster presentation. 2018.
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Annexes
Annex A List of tables Table 1: Total systemic antibiotics prescribed in humans from primary and secondary care and
quantity of antibiotics sold for use in food-producing animals in the UK, expressed in tonnes active
ingredient and percentage of the total; 2013–2017 ....................................................................... 11
Table 2: ESBL-/AmpC-producing E. coli in pig, broiler chickens and turkey caecal samples at
slaughter following selective culture in the UK; 2015–2017 ........................................................... 39
Table 3: E. coli resistance in retail beef and pork, and retail chicken in the UK; 2015–2017 .......... 41
Table 4: Published case studies of LA-MRSA from livestock and other animal species in the UK . 47
Table 5: Published reports of LA-MRSA from retail meat and animal products in the UK .............. 48
Table 6: Reported cases of CC398 LA-MRSA from humans in the UK ......................................... 49
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Annex B List of figures Figure 1: Proportion of tonnes of active ingredient prescribed for humans and sold for use in
animals in the UK; 2017 ................................................................................................................ 10
Figure 2: Year-over-year change in tonnes of active ingredient of HP-CIAs prescribed for humans
and sold for use in animals in the UK; 2013–2017 ........................................................................ 12
Figure 3: Quantity of antibiotics sold for use in food-producing animals for 30 European countries
as reported by ESVAC; mg active substance sold per population correction unit (mg/PCU); 2016 14
Figure 4: Consumption of antibiotics for systemic use (ATC group J01) in the community and
hospital sector in Europe as reported by ESAC-Net; 2017 ............................................................ 15
Figure 5: EU harmonised primary (total sales of veterinary antibiotics in mg/PCU) and secondary
(sales in mg/PCU for 3rd and 4th generation cephalosporins, quinolones and polymyxins) outcome
indicators for antibiotic consumption in food-producing animal species in the UK; 2013–2017 ...... 16
Figure 6: EU harmonised primary indicator: total consumption of antibiotics for systemic use in
humans (DDD per 1,000 inhabitants and per day) in the UK; 2013–2017 ..................................... 17
Figure 7: EU harmonised secondary indicators: ratio of the community consumption of broad-
spectrum penicillins, cephalosporins, macrolides (except erythromycin) and fluoroquinolones to the
consumption of narrow-spectrum penicillins, cephalosporins and erythromycin, and proportion of
total hospital antibiotic consumption that are glycopeptides, 3rd and 4th generation cephalosporins,
monobactams, carbapenems, fluoroquinolones, polymyxins, piperacillin and enzyme inhibitor,
linezolid, tedizolid and daptomycin (DDD per 1,000 inhabitants per day) in the UK; 2013–2017 ... 18
Figure 8: Recommended primary (proportion of fully susceptible E. coli isolates) and secondary
indicators (proportion of presumptive ESBL-/AmpC-producing E. coli isolates, proportion of
multiple-resistant E. coli isolates and proportion of E. coli isolates microbiologically resistant to
ciprofloxacin) for the animal AMR monitoring in the UK; 2014–2017 ............................................. 21
Figure 9: Recommended primary (proportion of 3rd generation cephalosporin-resistant E. coli
isolates and proportion of MRSA among S. aureus isolates) and secondary indicators (proportion
of K. pneumoniae resistant to fluoroquinolones, 3rd generation cephalosporins and
aminoglycosides, proportion of K. pneumoniae resistant to carbapenems, proportion of
S. pneumoniae resistant to penicillins and proportion of S. pneumoniae resistant to macrolides) for
the human health AMR monitoring in the UK; 2013–2017 ............................................................. 22
Figure 10: Percentage resistance (interpreted using EUCAST human CBPs) in C. jejuni isolates
from caecal samples taken at slaughter from broiler chickens and turkeys in the UK (EU
harmonised monitoring); 2014 and 2016 ....................................................................................... 23
Figure 11: Percentage resistance (interpreted using breakpoints) in C. jejuni and C. coli isolates
from retail chicken meat in the UK; 2014–2015 ............................................................................. 24
Figure 12: Percentage isolates with decreased-susceptibility (interpreted using EUCAST ECOFFs)
in C. jejuni and C. coli strains isolated from retail chicken meat in the UK; 2015–2017 ................. 25
Figure 13: Percentage susceptibility (interpreted using human EUCAST CBPs; non-susceptible:
resistant and intermediate) in routine laboratory surveillance reports of human Campylobacter spp.
isolates in the UK; 2013 (n=64,764) and 2017 (n=60,408) ............................................................ 26
Figure 14: Percentage resistance (interpreted using EUCAST human CBPs) in Salmonella spp.
obtained from broiler and layer chicken farms in the UK (National Control Plan/EU harmonised
AMR monitoring); 2014 and 2016 ................................................................................................. 29
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Figure 15: Percentage resistance (interpreted using EUCAST human CBPs) in Salmonella spp.
obtained from turkey farms in the UK (National Control Plan/EU harmonised AMR monitoring);
2014 and 2016 .............................................................................................................................. 29
Figure 16: Percentage resistance (interpreted using British Society for Antimicrobial Chemotherapy
(BSAC) human clinical break points where available, indicated with ‡) to selected antibiotics in
Salmonella Typhimurium isolates collected under the clinical surveillance programme from cattle,
pigs and chickens in England and Wales; 2013 and 2017 ............................................................. 31
Figure 17: Percentage susceptible and non-susceptible (intermediate and resistant) isolates
(interpreted using CBPs) in non-typhoidal Salmonella spp. from human faecal isolates (routine
laboratory surveillance reports) in the UK; 2013 (n=7,933) and 2017 (n=16,911) .......................... 32
Figure 18: Percentage resistance (interpreted using CBPs) in S. Typhimurium isolates from
humans reported through routine laboratory surveillance in England and Wales; 2013 (n=1,652)
and 2017 (n=2,424) ...................................................................................................................... 33
Figure 19: Percentage resistance (interpreted using EUCAST human CBPs) in E. coli isolated from
broiler chickens and turkeys in the UK (EU harmonised monitoring); 2014 and 2016 .................... 38
Figure 20: Percentage resistance (interpreted using EUCAST human CBPs) in E. coli isolated from
pigs in the UK (EU harmonised monitoring); 2015 and 2017 ......................................................... 38
Figure 21: Percentage resistance (interpreted using BSAC breakpoints where available; indicated
by ‡) in E. coli/coliform isolates collected under the clinical surveillance programme from cattle,
pigs, sheep, chickens and turkey in England and Wales; 2013 (n=1,400) and 2017 (n=810) ........ 40
Figure 22: Percentage susceptible and non-susceptible isolates (interpreted using CBPs) in human
E. coli blood isolates in the UK; 2013 (n=35,357) and 2017 (n=41,891) ........................................ 42
Figure 23: AMR systems map: influences on the development of AMR at top level, taken from
‘Antimicrobial Resistance (AMR) Systems Map Overview of the factors influencing the
development of AMR and the interactions between them’ ............................................................. 54
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Annex C Salmonella serovars
Annex Table C1: Top ten most isolated Salmonella serovars in the UK in humans and animals
(cattle, sheep, pigs, chickens, turkeys and ducks), 2013 and 201740.
Humans* Animals
Rank 2013 2017 Rank 2013** 2017
1. Enteritidis Enteritidis 1. Dublin Dublin
2. Typhimurium Typhimurium 2. Mbandaka Derby***
3. Infantis Typhimurium –
monophasic 3. Montevideo Mbandaka
4. Newport Newport 4. Senftenberg Senftenberg
5. Virchow Infantis 5. Kedougou Kedougou
6. Kentucky Agona 6. Derby*** 13,23:i:-
7. Stanley Stanley 7. Indiana Typhimurium
8. Agona Kentucky 8. 13,23:i:- Montevideo
9. Java Virchow 9. Typhimurium Indiana
10. Montevideo Java 10. Orion Give var. 15+
* All isolates: blood, urine and faecal; ** Isolates from England, Wales and Scotland only; *** Includes presumptive
S. Derby.
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Annex D Recommendations 2015 UK One Health report Recommendation 1
Public health organisations should work with clinical laboratory colleagues to ensure that all
Salmonella species are sent to the relevant reference laboratories for speciation and antibiotic
susceptibility testing. The referral form should include data on foreign travel, including countries
visited, in the previous four weeks.
Recommendation 2
Public health organisations should scope the development of a national sentinel surveillance
system for Campylobacter isolates collected from human infections. In addition, public health
organisations should highlight the importance of identifying Campylobacter to a species rather than
genus level, as different species have different antibiotic profiles.
Recommendation 3
Public health organisations should support the work of professional organisations to transition UK
clinical laboratories to a single standardised nationally agreed methodology for routine antibiotic
testing in 2016.
Recommendation 4
Public health organisations should work with professional organisations to develop guidance
related to recommended antibiotic and bacterial combinations, which should be tested and
reported by clinical laboratories for key One Health pathogens. Animal health organisations should
review the antibiotics tested from clinical veterinarian samples and through the EU harmonised
monitoring in animals to align with key antibiotics required for human treatment.
Recommendation 5
Human public health reference laboratories should follow the EU protocol for harmonised
monitoring of antibiotic resistance in human Salmonella and Campylobacter isolates.
Recommendation 6
Public health organisations should explore data available on human sales of antibiotics from
manufacturers and holders of human antibiotic marketing authorisations.
Recommendation 7
The Veterinary Medicines Directorate (VMD) will conduct carbapenem resistance monitoring (as
part of the EU monitoring and reporting of antibiotic resistance in zoonotic and commensal bacteria
in accordance with the EU legislation, Commission Decision 2013/652/EU), a year earlier than
mandated.
Recommendation 8
VMD will participate in the protocol development of the European Surveillance Veterinary Antibiotic
Consumption (ESVAC) project to collect farm level data from the pig sector; and investigate and
facilitate options for collecting accurate antibiotic consumption data at an individual farm level.
Recommendation 9
Public and professional One Health activities should be enhanced through engagement with the
European Antibiotic Awareness Day (EAAD) campaign and aligning training programmes for
human and animal health professionals.
Recommendation 10
The human and animal surveillance bodies should produce a further report in two years,
encompassing robust data collected by the Food Standards Agency (FSA) on the burden of AMR
in imported food animals.
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Annex E Sources and caveats/limitations of consumption data
Human data
Human antibiotic prescribing is based on the data submitted by the UK to the European
Antimicrobial Consumption Surveillance Network (ESAC-Net). Data were collected for community
(primary care) and hospital (secondary care and tertiary care) as the number of Daily Defined
Doses (DDD) per the WHO’s Anatomical Therapeutic Chemical (ATC) classification substance and
route of administration. For the purpose of this report, antibiotics for systemic use and intestinal
antibiotics ([ATC] groups J01, A07AA) were included, expressed as tonnes of active compound.
Data were not available from private prescriptions dispensed in the community and private
hospitals. Primary care data are available at a patient level in Scotland, Wales and Northern
Ireland and aggregated at a General Practice level in England. Hospital data are aggregated
dispensed data to wards and patients.
The WHO’s ATC classification system was also used for assigning weights of active ingredient.
Animal data
Annual sales data of all authorised antibiotic veterinary medicinal products are provided to VMD by
the marketing authorisation holders, in accordance with the Veterinary Medicines Regulations 2013
(S. I. 2013 No. 2033), schedule 1, paragraph 31 (3a). The weight of active substance sold is an
exact measurement following from the quantitative composition of active ingredient for each
product and the number of units sold. For the purpose of this report, antibiotics of ATCvet groups
QJ01, QJ51 and QA07AA were included. Sales of dermatological preparations and preparations
for sensory organs are not included.
It is not possible to calculate accurate data on antibiotic sales at the animal species level or
production category from the overall sales data, as antibiotic veterinary products often are
authorised for use in more than one animal species and therefore it is not possible to know in
which species the product sold was used.
Use based on sales data is often over estimated as for example not all antibiotics sold will be used
(due to natural wastage, or reaching expiry date), or some products are sold to UK feed mills which
exports the feed after adding those products.
Medicinal products sold for use in humans but used in animals according to the prescribing
cascade are not included in the overall sales data.
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Annex F Methodology AMR data
Human data
Human clinical specimens tested in clinical diagnostic laboratories are grouped into 14 day-patient-
organism episodes, where follow-up specimens (where the same organism is identified) within
14 days are excluded. Antibiotic susceptibility tests are collated and the most resistant result for an
antibiotic within that 14 day episode is retained. Clinical diagnostic laboratories use clinical
breakpoints to determine a susceptibility result of ‘susceptible’, ‘intermediate’ or ‘resistant’, as
determined according to test method and published breakpoints (EUCAST, BSAC or CLSI),
manual laboratory methods (e.g. disc diffusion) or automated diagnostic systems (e.g. Vitek).
Results are presented as ‘non-susceptible’ which is the sum of those that are resistant and those
that are reported as intermediate.
The reference laboratories assess resistance according to clinical breakpoint, as well as using
epidemiological cut offs (ECOFF). Harmonised monitoring of Salmonella and Campylobacter spp.
from human samples within the EU determines which breakpoints are used for international
publication.w
UK reports to ECDC for the annual zoonoses report used within the international comparison
summaries are made by the reference laboratory. Data for the harmonised indicators were
obtained from the ECDC Surveillance Atlas reflecting UK data through the Ears-Net surveillance
programmes. This surveillance does not include all laboratories within the UK.
England
Data on microorganism and antibiotic susceptibility for England were obtained for routine
diagnostic specimens from the PHE national communicable disease and antibiotic resistance
reporting system SGSS (Second Generation Surveillance System)78. Data on blood
(Campylobacter spp. and E. coli) and faecal (Salmonella spp. and Campylobacter spp.) specimens
were obtained from the communicable disease reporting (CDR) module of SGSS. Additional
Campylobacter and Salmonella information was obtained from the PHE Gastrointestinal Bacteria
Reference Unit (GBRU) based on samples referred to the Unit.
Campylobacter isolates are sent to the reference laboratory when there is a public health response
to a potential outbreak or where the clinical laboratory wishes to identify at species level and
confirm antibiotic susceptibilities. Less than 1% of clinical Campylobacter isolates are sent to the
reference laboratory.
Scotland
Microorganism and antibiotic susceptibility testing data were obtained from all clinical diagnostic
laboratories in Scotland and participating reference laboratories via ECOSS (Electronic
Communication of Surveillance in Scotland), an electronic data link from microbiology laboratories
to Health Protection Scotland (HPS).
Faecal samples are not routinely received by HPS, sample size is therefore very small and
susceptibility data are not representative of national data. During 2016 ampicillin susceptibility
testing changed to the combination ampicillin/amoxicillin
w https://ecdc.europa.eu/sites/portal/files/media/en/publications/Publications/antimicrobial-resistance-Salmonella-
Campylobacter-harmonised-monitoring.pdf
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For Salmonella blood samples, the only cephalosporin tested is cefotaxime, and no carbapenem
(meropenem/imipenem) is tested.
Northern Ireland
Northern Ireland microorganism and antibiotic susceptibility data were retrieved from CoSurv, the
electronic system by which all clinical diagnostic laboratories in Northern Ireland reported
voluntarily to the Public Health Agency from their own laboratory information systems.
E. coli blood isolate susceptibility information is only available for ciprofloxacin and gentamicin
Wales
Microorganism and antibiotic susceptibility data for Wales were retrieved from the Welsh DataStore
systems. DataStore collects all data stored on the hospital information systems and maps into a
pseudo-anonymised standardised format.
Salmonella information was obtained from the PHE GBRU based on samples referred to the Unit.
Susceptibility information for faecal isolates in 2017 was not available at time of compilation.
Animal data
EU harmonised AMR monitoring
In accordance with the EU harmonised AMR monitoring (as set out in Commission Implementing
Decision 2013/652/EU) the UK government monitors antibiotic resistance in zoonotic and
commensal bacteria from healthy food-producing animals at slaughter and fresh meat at retail.
Samples are collected at alternating years for poultry (turkey and broilers) and pig populations.
This is a programme carried out in the UK and data collected through this programme are
considered to be more relevant to public health and better reflect the potential exposure of humans
to AMR from animals and food.
VMD is the national competent authority for AMR in animals and therefore coordinates the EU
harmonised monitoring for the UK. FSA personnel collect the samples for monitoring E. coli and
C. jejuni at the slaughterhouse for England, Scotland and Wales and at retail for the UK; DAERA
coordinates the caecal sample collection in Northern Ireland. Samples are subsequently tested and
analysed by APHA for England, Scotland and Wales and by AFBI for Northern Island. Retail
samples obtained for specific monitoring of ESBL-/AmpC-/carbapenemase-producing E. coli are
tested by APHA for the UK, Campylobacter spp. isolated from retail meat were tested by PHE
laboratories.
E. coli are isolated (n = 170 for each animal species) from caecal samples at slaughter. In addition,
specific samples from caecal contents at slaughter and fresh meat at retail (n = 300 for each
animal species and type of sample) are tested for presence of ESBL-/AmpC-/carbapenemase-
producing E. coli. C. jejuni are isolated (n = 170 for each animal species) from caecal samples
from broilers and fattening turkeys.
Susceptibility testing is performed against a panel of antibiotics defined by the EU and using a
standardised broth microdilution method. In addition, samples collected for specific ESBL-/AmpC-/
carbapenemase-producing E. coli monitoring are cultured on MacConkey agar + 1 mg/L
cefotaxime to isolate ESBL-/AmpC-/carbapenemase-producing E. coli, on CHROMagar to isolate
ESBL-producing E. coli, and onto chromID CARBA and chromID OXA-48 agars to isolate
carbapenemase-producing E. coli. E. coli isolates from samples collected in GB are also cultured
on MacConkey agar + 2 mg/L colistin.
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Salmonella isolates are obtained from boot swabs/dust samples collected on farm for each
population of laying hens, broilers and fattening turkeys under the National Control Plan and sent
to APHA for further testing. In addition, carcase neck skin samples of broilers and fattening turkeys
and carcase swabs from pigs are taken by food business operators at slaughter. Private
laboratories perform bacteriological culture on these samples for presence of Salmonella and are
asked to submit isolates to APHA for serotyping and antibiotic susceptibility testing.
Susceptibility is interpreted using EUCAST human clinical break point (CBP) values and EUCAST
epidemiological cut-off values (ECOFFs).
Clinical surveillance
In addition to the EU harmonised AMR monitoring, the UK performs passive surveillance which
evaluates AMR in veterinary pathogens isolated from diagnostic samples from field cases of
clinical disease undergoing investigation. The samples are submitted by private veterinary
surgeons to APHA veterinary laboratories in England and Wales for identification of a potential
bacterial pathogen and subsequent susceptibility testing to provide the veterinarian with relevant
information for treatment. Similar programmes are conducted in Scotland (SRUC Veterinary
Services) and Northern Ireland (AFBI). This surveillance programme also includes susceptibility
testing of Salmonella isolates recovered from animals and their environment in GB, as part of the
UK Zoonoses Order 1989.
In principle, susceptibility testing is performed using a disc diffusion method on Iso-Sensitest Agar
(Oxoid) with appropriate media supplementation, where necessary, for fastidious organisms,
following guidelines by the British Society for Antibiotic Chemotherapy (BSAC). Resistance is
determined using BSAC human clinical breaking points. When no published BSAC breakpoints are
available, historical APHA veterinary breakpoints are used. Clinical isolates obtained under the
framework of the clinical surveillance programme are tested for resistance using a disc diffusion
method; since 2016 APHA routinely implements a pre-diffusion method to test for colistin
resistance.
Food data
EU harmonised AMR monitoring in retail meat
The European Commission has set-up a 7-year mandatory Member State surveillance (2014-
2020) for antibiotic resistance in specific pathogens in food-production animals within
slaughterhouse environments. The FSA is leading on an additional component of this survey by
analysing retail meats (beef, pork and poultry) in the UK for ESBL-, AmpC- and carbapenemase-
producing E. coli. Testing for colistin resistance and the colistin resistance genes (mcr-1, mcr-2)
has also been included since January 2016. As the FSA is undertaking this survey on behalf of the
EC, the Commission’s Decision in relation to scope, sampling methodology, analytical methods
and reporting of data must be adhered to.
Although the survey commenced in 2014, there was no requirement to take retail samples for AMR
in the first year. The sampling regimes are outlined below:
300 beef and 300 pork retail samples to be collected/tested in 2015, 2017 and 2019.
300 poultry meat retail samples to be collected/tested in 2016, 2018 and 2020.
Sampling represents 80% retail market share and 80% population coverage of the four countries of
the UK; sampled proportionally throughout the full year. Analysis requires initial isolation and
enrichment of E. coli from all meat samples, prior to testing for AMR E. coli. Analysis is performed
in a step-wise process against a two-tier panel of antibiotic agents depending on the presence of
positive isolates. Data collected by the testing facility is submitted to the EFSA on an annual basis
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in May following each year of completion; aggregated to UK datasets with no identification of retail
names or product brands.
AMR Campylobacter Retail Chicken Survey
The FSA has carried out several microbiological surveys of Campylobacter contamination in fresh
whole UK-produced chilled chickens at retail sale. As part of this survey, a subset of the
Campylobacter isolates collected has been tested for their resistance to a range of antibiotic
agents.
A first overall survey tested 4,011 samples of whole, UK-produced fresh chicken during the period
February 2014 to March 2015 (Year 1). The samples were evenly distributed throughout the year
and the UK (in proportion to population size of each country), and testing was performed by six
laboratory sites. Retailers were sampled in proportion to their market share, according to available
data, with their share of free range, organic and standards chickens taken into account.
A subset (283) of the Campylobacter isolates was tested for antibiotic resistance. These were
selected as every tenth isolate (or next viable isolate) but selection was adjusted to ensure
adequate representation of producer premises and retailers. All recoverable organic and free range
chicken isolates were included. The objective of the AMR analysis was to establish the proportion
of C. jejuni and C. coli strains isolated from Year 1 of the retail chicken survey that were resistant
to a range of antibiotic agents relevant to public health.
To determine resistance, Iso-Sensitest Agar with the addition of 5% horse blood containing
specified breakpoint concentrations of antibiotics was used. An isolate suspension was made in
brain heart infusion broth to McFarland 0.5 turbidity and was inoculated onto the surface of each of
the antibiotic containing agars. An isolate was considered resistant if it grew on the agar and
scored susceptible if there was no growth, and the corresponding antibiotic free plate showed pure
growth from the suspension. AMR profiles were determined using the following antibiotics and
concentrations as described in 25:
Chloramphenicol 8 mg/L, 16 mg/L Ciprofloxacin 1 mg/L (CpL), 5 mg/L (CpH) Erythromycin 4 mg/L (EryL), 16 mg/L (EryH) Gentamicin 1 mg/L, 2 mg/l, 4 mg/L (GH) Kanamycin 16 mg/L (K) Nalidixic acid 16 mg/L (NalL), 32 mg/L (NalH) Neomycin 8 mg/L (Ne) Streptomycin 2 mg/L (SL), 4 mg/L (SH) Tetracycline 2 mg/L (TetL), 8 mg/L (TetII), 128 mg/L (TetH) Trimethoprim 2 mg/L
A second survey (Year 2) tested 2,998 samples of whole, UK-produced fresh chicken during the
period July 2015 to March 2016. A pilot study was also carried out from April 2016 to July 2016 to
assess a new sampling methodology. Approximately 416 chilled chickens were sampled and
tested during this pilot period. The samples for the main survey were evenly distributed throughout
the year and the UK, and retailers were sampled with their share of free-range, organic and
standard chickens taken into account.
A subset (548) of the Campylobacter isolates was tested for antibiotic resistance. These were
selected as every tenth isolate (or next viable isolate) but selection was adjusted to ensure
adequate representation of producer premises and retailers. All recoverable organic and a high
proportion of free range chicken isolates were included.
To determine resistance, Muller Hinton Agar with the addition of 5% horse blood containing
specified breakpoint concentrations of antibiotics was used. An isolate suspension was made in
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sterile saline to McFarland 0.5 turbidity and was inoculated onto the surface of each of the
antibiotic containing agars. An isolate was considered resistant if it grew on the agar and scored
susceptible if there was no growth, and the corresponding antibiotic free plate showed pure growth
from the suspension. AMR profiles were determined using the epidemiological cut-off (ECOFF)
values as recommended in the ECDC EU protocol for harmonising monitoring of AMR in human
Salmonella and Campylobacter isolates 33
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Annex G Caveats/limitations of AMR data
Human data
The four UK health administrations have similar methods for data collection of antibiotic resistance
in human isolates, although there are differences in how these are managed. For the majority of
bacteria resistance is collected through passive surveillance systems, collecting microbiology
results from clinical laboratories. Additional information is collected through reference laboratory
surveillance. Over 70% of E. coli bacteraemia and Salmonella infections have antibiotic
susceptibility testing results available. However, less than 50% of Campylobacter isolates have
susceptibility testing and where this is performed it is predominantly limited to erythromycin and
ciprofloxacin. Less than 1% of Campylobacter isolates are sent to the Reference laboratory, where
they are tested against a wide array of antibiotics.
Different antibiotic susceptibility testing methodologies are used in England and Wales, Scotland,
and Northern Ireland. England, Wales and Scotland utilise the BSAC/EUCAST methodology to
determine resistance/susceptibility to an antibiotic based on human clinical breakpoints, whilst in
Northern Ireland, an accredited CLSI method utilising different antibiotic concentrations is used for
testing. The amalgamated results of such UK wide monitoring should be interpreted with caution.
There was a phased transition by the Scottish diagnostic laboratories from CLSI to EUCAST
breakpoints in 2012 – 2013. In Wales, all microbiology laboratories are currently moving to
EUCAST AST methodology and previously used BSAC methodology.
Testing for presence of ESBL and/or AmpC is not routinely undertaken in clinical laboratories, but
rather some laboratories with capacity will test for presence if key criteria have been met (such as
patient risk factors and phenotypic resistance profile of the specimen). This selective testing
increases the likelihood of ESBL and/or AmpC presence in the subset tested.
Campylobacter AMR from human samples presented within this report combines faecal and blood
isolate reports. AMR in Salmonella isolates from human samples presented in this report are from
faecal samples only. Resistance summaries in E. coli human isolates use blood samples only.
Additional detail on specimen type and antimicrobial are available in Annex Tables F1–2.
Annex Table F1: Antimicrobial susceptibility test data by sample type and pathogen by devolved
administration (England [E]; Northern Ireland [NI]; Scotland [S]; Wales [W])
Campylobacter sp. Campylobacter coli Campylobacter jejuni
Blood Faecal Blood Faecal Blood Faecal
E NI S W E NI S W E NI S W E NI S W E NI S W E NI S W
Ciprofloxacin * * *
* * *
* * *
* * *
Nalidixic acid *
*
* * *
* * *
* * *
Erythromycin * * *
* * *
* * *
* * *
Gentamicin *
*
* * *
* * *
* * *
Streptomycin *
*
* * *
* * *
* * *
Chloramphenicol *
*
* * *
* * *
* * *
Tetracyclines *
*
* * *
* * *
* * *
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Annex Table F2: Antimicrobial susceptibility test data by sample type and pathogen by devolved
administration (England [E]; Northern Ireland [NI]; Scotland [S]; Wales [W])
Salmonella spp. Escherichia coli
Blood Faecal Blood Faecal
E NI S W E NI S W E NI S W E NI S W
Amikacin * *
Ampicillin * * * * *
Cefotaxime * * * * *
Cefoxitin * *
Ceftazidime * * * *
Chloramphenicol * * * * *
Ciprofloxacin * * * * * *
Colistin * * * *
Ertapenem * *
Erythromycin * * * *
Gentamicin * * * * *
Meropenem * * * *
Nalidixic acid * * * * *
Neomicin * *
Streptomycin * * *
Sulphonamides * * * * *
Tetracycline * * * * *
Tigecycline * * * *
Tobramycin * *
Trimethoprim * * * * *
Animal data
The ECOFF represents the value where bacteria have developed a higher level of resistance to
that antibiotic than the background level of resistance that exists naturally for that bacterial species;
this does not necessarily correspond with likelihood of clinical treatment failure.
The use of selective culture methods leads to a greater sensitivity for assessing occurrence of
ESBL-, AmpC- and carbapenemase-producing E. coli than the use of non-selective culture
methods. Selective methods are used to detect low numbers of resistant E. coli, but do not permit
quantitation
Only small numbers of Salmonella isolates originating from neck skin samples taken by food
business operators are tested for susceptibility, and these results are not likely to be representative
and should be interpreted with caution.
Sampling performed under the clinical (passive) surveillance system, is not considered
representative for the general livestock population and results should be interpreted with caution. It
should be noted that these E. coli are isolated from samples from field cases and tested for
diagnostic purposes, meaning that these are most often isolated from sick animals. It is unknown
whether these samples are collected pre- or post-treatment, and these results should be
interpreted with caution. This is a biased population and cannot be considered to accurately reflect
the bacterial populations present within the general animal population in the UK. Further, veterinary
surgeons have the option to submit samples to private laboratories. The proportion of samples that
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Government laboratories test compared to other laboratories is not known, and therefore
representativeness of the samples processed by APHA, SRUCVS, and AFBI is unknown.
Geographical proximity of a farm or veterinary practice to a Government diagnostic laboratory has
an impact on the submission rate of samples; clinical surveillance may therefore over‐represent the
animal populations within certain geographical areas.
The levels of resistance demonstrated by the clinical surveillance isolates presented in this report
may be higher than those seen in the wider bacterial populations present within animals in England
and Wales. This is because samples from diseased animals may be submitted from animals that
have been unresponsive to initial antibiotic therapy, and thus the isolates recovered may have
already been exposed to antibiotic pressure(s).Isolates from companion animals, which are
submitted to APHA are only investigated for antibiotic resistance if there is a public health concern,
and therefore bacteria from these animal groups are under‐represented in this report. The
veterinary clinical surveillance data detail the number of bacterial isolates that underwent
susceptibility testing, but not the numbers of animals for which samples were submitted for
examination. Several bacteria may have been cultured from an individual animal or from a group of
animals on the same farm. This type of clustering is not accounted for in the report, though since
only low numbers of bacteria are usually subjected to susceptibility testing from the same outbreak
of disease, its importance is probably limited.
The diagnostic tests performed on any sample received through the clinical surveillance
programme are dependent on the individual case; i.e. isolates of the same bacterial species are
not always tested against the same panel of antibiotics. Therefore, if resistance is not detected in
one isolate, it may not mean that resistance is not present, just that it was not tested for. This is
especially true of commensal organisms.
The breakpoints used for determining resistance for isolates recovered under the veterinary clinical
surveillance programme in GB are those as recommended by BSAC. These breakpoints were
originally determined for human medicine and their use in veterinary medicine is based on the
assumption that the concentration of antibiotic at the site of infection is approximately the same in
animals as it is in humans. Currently it is not known if this assumption is always correct.
Different antibiotic susceptibility testing methodologies are used in England & Wales (APHA),
Scotland (SRUCVS), and Northern Ireland (AFBI). APHA and SRUCVS use BSAC methodology to
determine resistance/susceptibility based on human clinical breakpoints, whilst AFBI use CLSI. In
light of the different methodologies and breakpoints used, the amalgamated results of UK wide
monitoring should be interpreted with caution.
For AST testing done by APHA, in the case of some veterinary drug/bug combinations a BSAC
cut‐off may not exist. In this case, APHA may have derived a tentative or suggested breakpoint or
the historical veterinary breakpoint (zone size cut‐off of resistant <=13mm) may have been used to
define resistance.
E. coli isolates are not collected from routine samples from healthy livestock in Northern Ireland.
Only clinical cases submitted for post-mortem investigation when colibacillosis, or similar diseases,
will proceed to isolate pathogenic E. coli. AMR testing on E. coli isolates is mainly performed if
samples are coming from less than 2-week old calves and animals with bovine mastitis.
With regards to E. coli, each organisation in the United Kingdom sets their own criteria for testing
AMR in E. coli from clinically sick animals and these criteria are not uniform. This is pertinent to
highlight as the selection of isolates for susceptibility testing based on age or other criteria can
influence the result obtained.
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Annex H Human biomass and Population Correction Unit
Human biomass
Data on the UK human population were taken from Population Estimates Summary for the UK,
mid-2017, Office for National Statistics. The following body weights were used to estimate human
biomass79: a body weight of 70 kg was used for adults aged above 18 years, a body weight of 40
kg was used for children aged 4-17 years, a body weight of 12 kg for children aged 1-3 years and a
body weight of 5 kg was used for infants aged 0- 12 months.
Population correction unit (PCU)
Trends in sales of antibiotics over time are determined by taking into consideration variations in the
size and number of the animal population. This is achieved by using a population correction unit
(PCU). The PCU is a technical unit of measurement formulated by the EMA and adopted by the
ESVAC project to standardise sales data against an animal population denominator.
The PCU is calculated by multiplying a standardised average weight at time of treatment with the
associated annual animal/slaughter numbers. The calculation also takes into account animals
exported from the UK to EU countries for slaughter and imported from EU countries to the UK for
fattening. These data are provided by ESVAC and obtained from Eurostat (statistical office of the
EU) and TRACES (Trade Control and Expert System of the EU) and validated by reports supplied
by Defra and Cefas. For more information on the calculation and the PCU, please see the
document provided on the UK Government’s website:
https://www.gov.uk/government/publications/understanding-the-mgpcu-calculation-used-for-
antibiotic-monitoring-in-food-producing-animals and the ESVAC website:
https://www.ema.europa.eu/en/veterinary-regulatory/overview/antimicrobial-resistance/european-
surveillance-veterinary-antimicrobial-consumption-esvac#population.
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Annex I Highest Priority Critically Important Antibiotics for human and veterinary medicine
WHO – critically important antibiotics for human medicine
The WHO has developed criteria and subsequently applied these to rank antibiotic classes
according to their importance in human medicine. The criteria are80:
“The antimicrobial class is the sole, or one of limited available therapies, to treat serious
bacterial infections in people.”
“The antimicrobial class is used to treat infections in people caused by either: (1) bacteria
that may be transmitted to humans from nonhuman sources, or (2) bacteria that may
acquire resistance genes from nonhuman sources.”
Antibiotic classes meeting both criteria are classified as critically important antibiotics for human
medicine. Within this category certain antibiotics are subsequently classified as highest priority,
and these are included in Annex Table I1.
AMEG – category 2
The Antimicrobial Advice ad hoc Expert Group (AMEG) of the EMA provided guidance on the
impact on public health and animal health of the use of antibiotics in animals, and on the measures
to manage the possible risk to humans. As part of this guidance the AMEG ranked the antibiotics
classified by WHO as CIAs according to the degree of risk to man due to resistance development
following use in animals, thereby taking a One Health approach4, 5. If that risk was estimated to be
higher, antibiotics were classed as category 2 (with category 1 being low or limited risk). These
antibiotic classes are included in Annex Table I1. In this report the classification according to
AMEG is used.
Annex Table I1: Overview of antibiotic classes classified as Highest Priority Critically Important
Antibiotics (HP-CIAs) for human medicine by WHO and category 2 by the AMEG
WHO – HP-CIA AMEG – category 2
Colistin Colistin
Fluoroquinolones Fluoroquinolones
Quinolones
3rd and 4th generation cephalosporins 3rd and 4th generation cephalosporins
5th generation cephalosporins
Macrolides
Ketolides
Other polymyxins
Glycopeptides
WHO/England – AWaRE categories
The WHO recently updated the Essential Medicines List (EML) and classified key antibiotics into
three categories (AWaRe): to improve access (Access), to monitor important antibiotics (Watch)
and to preserve effectiveness of ‘last resort’ antibiotics (Reserve).
Adaptation of the AWaRe list for England was achieved using expert elicitation for the antibiotics
that were not in the EML categories. In addition, given a national priority to reduce use of
piperacillin/tazobactam and carbapenems, these were moved from Access into Watch and
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Reserve categories respectively. In total, the status of 38 antibiotics was changed between the
WHO AWaRe list and the adapted list for England (Annex Figure I1).
Annex Figure I1: Overview of antibiotic substances categorized according to AWaRE (Access,
Watch, Reserve) according to WHO and PHE81
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Annex J Glossary of terms Active ingredient The part of an antibiotic medicine that acts against the bacterial
infection. Alternatively called ‘active substance’.
AFBI Agri-Food and Biosciences Institute, Northern Ireland
AMEG Antimicrobial Advice ad hoc Expert Group; AMEG is an ad hoc group established by the European Medicines Agency jointly under the Committee for Medicinal Products for Veterinary Use (CVMP) and the Committee for Medicinal Products for Human Use (CHMP). The AMEG was set up to provide guidance on the impact on public health and animal health of the use of antibiotics in animals, and on the measures to manage the possible risk to humans.
AMR Antibiotic Resistance/Antimicrobial Resistance
AMRHAI Antimicrobial Resistance and Healthcare Associated Infections Reference Unit
APHA Animal and Plant Health Agency; an executive agency for Defra, the Scottish Government and the Welsh Government.
ATC Anatomical Therapeutic Chemical Classification System
ATCvet Anatomical Therapeutic Chemical Classification System for veterinary medicinal products
Antibiotic A large group of antibacterial substances capable of destroying or inhibiting the growth of bacteria, used for treatment or prevention of bacterial infections.
Antimicrobial Naturally occurring, semi-synthetic or synthetic substances that exhibit antimicrobial activity (kill or inhibit the growth of micro-organisms). Used for treatment or prevention of infections. Antimicrobials include antibacterials (antibiotics), antivirals, antifungals and antiprotozoals.
Antibiotic/antimicrobial resistance
The ability of a micro-organism/bacterium to grow or survive in the presence of an antimicrobial that is usually sufficient to inhibit or kill micro-organisms of the same species.
Antibiotic Stewardship Antibiotic stewardship is a key component of a multifaceted approach to preventing emergence of antibiotic resistance. Good antibiotic stewardship involves selecting an appropriate drug and optimising its dose and duration to cure an infection while minimising toxicity and conditions for selection of resistant bacterial strains.
AST Antibiotic susceptibility testing: using laboratory methods to determine whether a bacterium is susceptible to a drug in vitro.
Bacteraemia The presence of bacteria in the bloodstream.
BPC British Poultry Council
BSAC British Society for Antibiotic Chemotherapy
CBP Clinical Break Point: relates the laboratory results to the likelihood of clinical treatment success or failure.
Cefas Centre for Environment, Fisheries and Aquaculture Science
Critically Important Antibiotics
These are antibiotic classes, which are the sole or one of limited available therapies, to treat serious bacterial infections in people and are used to treat infections caused by bacteria that may be transmitted to humans from non-human sources or, bacteria that may acquire resistance genes from non-human sources (WHO definition).
DAERA Department of Agriculture, Environment and Rural Affairs, Northern Ireland
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DHSC Department of Health and Social Care
Defra Department for Environment, Food and Rural Affairs
ECDC European Centre for Disease Prevention and Control
ECOFF Epidemiological cut-off value: represents the point at which bacteria have developed a higher level of resistance to an antibiotic than the background level of resistance that exists naturally for that bacterial species. A ‘resistant’ (or ‘non-susceptible’) ECOFF does not necessarily imply a level of resistance which would correspond with clinical treatment failure.
EFSA European Food Safety Authority
EMA European Medicines Agency
ESVAC European Surveillance of Veterinary Antimicrobial Consumption
EUCAST European Committee on Antimicrobial Susceptibility Testing
Eurostat Eurostat is the statistical office of the European Union
Food-producing animal (species)
Animals used for food production including (but not limited to): cattle, sheep, pigs, poultry, salmon, trout and bees.
FSA Food Standards Agency
HP-CIA Highest Priority Critically Important Antibiotics. In this report the classification according to the AMEG has been used; therefore the following classes of antibiotics are included under HP-CIAs: fluoroquinolones, 3rd and 4th generation cephalosporins and colistin.
HPS Health Protection Scotland
MIC Minimum Inhibitory Concentration: the lowest concentration of an antibiotic that inhibits visible growth of a bacterium after overnight incubation.
Non-food-producing animal (species)
Animals not reared for food. These are mainly companion animals including (but not limited to): dogs, cats, horses, small mammals, rabbits and birds.
NRL National Reference Laboratory
OIE World Organisation for Animal Health
PHE Public Health England
Population Correction Unit (PCU)
This is a technical unit of measurement which is used to represent the estimated weight at treatment of livestock and slaughtered animals. It takes into account a country’s animal population over a year, along with the estimated weight of each particular species at the time of treatment with antibiotics. 1 PCU = 1 kg of different categories of livestock and slaughtered animals.
SG Scottish Government
TARGET Treat Antibiotics Responsibly, Guidance, Education, Tools
TRACES The 'TRAde Control and Expert System' (TRACES) is the European Commission’s online management tool for all sanitary requirements on intra-EU trade and importation of animals, semen and embryo, food, feed and plants.
VMD Veterinary Medicines Directorate, an Executive Agency of Defra.
WG Welsh Government
WHO World Health Organization